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Erschienen in: Tumor Biology 8/2016

14.05.2016 | Review

Significance of oncogenes and tumor suppressor genes in AML prognosis

Erschienen in: Tumor Biology | Ausgabe 8/2016

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Abstract

Acute myeloid leukemia (AML) is a heterogeneous disorder among hematologic malignancies. Several genetic alterations occur in this disease, which cause proliferative progression, reducing differentiation and apoptosis in leukemic cells as well as increasing their survival. In the genetic study of AML, genetic translocations, gene overexpression, and mutations effective upon biology and pathogenesis of this disease have been recognized. Proto-oncogenes and tumor suppressor genes, which are important in normal development of myeloid cells, are involved in the regulation of cell cycle and apoptosis, undergo mutation in this type of leukemia, and are effective in prognosis of AML subtypes. This review deals with these genes, the assessment of which can be important in the diagnosis and prognosis of patients as well as therapeutic outcome.
Literatur
1.
Zurück zum Zitat Grimwade D. The changing paradigm of prognostic factors in acute myeloid leukaemia. Best Pract Res Clin Haematol. 2012;25(4):419–25.PubMed Grimwade D. The changing paradigm of prognostic factors in acute myeloid leukaemia. Best Pract Res Clin Haematol. 2012;25(4):419–25.PubMed
2.
Zurück zum Zitat Dash A, Gilliland DG. Molecular genetics of acute myeloid leukaemia. Best Pract Res Clin Haematol. 2001;14(1):49–64.PubMed Dash A, Gilliland DG. Molecular genetics of acute myeloid leukaemia. Best Pract Res Clin Haematol. 2001;14(1):49–64.PubMed
3.
Zurück zum Zitat Lo-Coco F, Breccia M, Noguera N, Miller Jr WH. Diagnostic value of detecting fusion proteins derived from chromosome translocations in acute leukaemia. Best Pract Res Clin Haematol. 2003;16(4):653–70.PubMed Lo-Coco F, Breccia M, Noguera N, Miller Jr WH. Diagnostic value of detecting fusion proteins derived from chromosome translocations in acute leukaemia. Best Pract Res Clin Haematol. 2003;16(4):653–70.PubMed
4.
Zurück zum Zitat De Jonge H, Huls G, De Bont E. Gene expression profiling in acute myeloid leukaemia. Neth J Med. 2011;69(4):167–76.PubMed De Jonge H, Huls G, De Bont E. Gene expression profiling in acute myeloid leukaemia. Neth J Med. 2011;69(4):167–76.PubMed
5.
Zurück zum Zitat Ramos NR, Mo CC, Karp JE, Hourigan CS. Current approaches in the treatment of relapsed and refractory acute myeloid leukemia. J Clin Med. 2015;4(4):665–95.PubMedPubMedCentral Ramos NR, Mo CC, Karp JE, Hourigan CS. Current approaches in the treatment of relapsed and refractory acute myeloid leukemia. J Clin Med. 2015;4(4):665–95.PubMedPubMedCentral
6.
Zurück zum Zitat Villela L, Bolaños-Meade J. Acute myeloid leukaemia: optimal management and recent developments. Drugs. 2011;71(12):1537–50.PubMedPubMedCentral Villela L, Bolaños-Meade J. Acute myeloid leukaemia: optimal management and recent developments. Drugs. 2011;71(12):1537–50.PubMedPubMedCentral
7.
Zurück zum Zitat Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Hematology/oncology clinics of North America. 2010;24(1):35–63.PubMed Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Hematology/oncology clinics of North America. 2010;24(1):35–63.PubMed
8.
Zurück zum Zitat Willman CL, Whittaker MH. The molecular biology of acute myeloid leukemia. Proto-oncogene expression and function in normal and neoplastic myeloid cells. Clin Lab Med. 1990;10(4):769–96.PubMed Willman CL, Whittaker MH. The molecular biology of acute myeloid leukemia. Proto-oncogene expression and function in normal and neoplastic myeloid cells. Clin Lab Med. 1990;10(4):769–96.PubMed
9.
Zurück zum Zitat Lyman SD, Jacobsen SEW. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91(4):1101–34.PubMed Lyman SD, Jacobsen SEW. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91(4):1101–34.PubMed
10.
Zurück zum Zitat Mizuki M, Schwäble J, Steur C, Choudhary C, Agrawal S, Sargin B, et al. Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood. 2003;101(8):3164–73.PubMed Mizuki M, Schwäble J, Steur C, Choudhary C, Agrawal S, Sargin B, et al. Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood. 2003;101(8):3164–73.PubMed
11.
Zurück zum Zitat Bullinger L. New avenues for genetics guided therapeutic approaches in AML. Acta Haematol Pol. 2014;45(4):322–9. Bullinger L. New avenues for genetics guided therapeutic approaches in AML. Acta Haematol Pol. 2014;45(4):322–9.
12.
Zurück zum Zitat Martens JH, Stunnenberg HG. The molecular signature of oncofusion proteins in acute myeloid leukemia. FEBS Lett. 2010;584(12):2662–9.PubMed Martens JH, Stunnenberg HG. The molecular signature of oncofusion proteins in acute myeloid leukemia. FEBS Lett. 2010;584(12):2662–9.PubMed
13.
Zurück zum Zitat Redner RL, Wang J, Liu JM. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood. 1999;94(2):417–28.PubMed Redner RL, Wang J, Liu JM. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood. 1999;94(2):417–28.PubMed
14.
Zurück zum Zitat Brown N, Ramalho M, Pedersen EW, Moravcsik E, Solomon E, Grimwade D. PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders? Front Biosci (Landmark edition). 2008;14:1684–707. Brown N, Ramalho M, Pedersen EW, Moravcsik E, Solomon E, Grimwade D. PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders? Front Biosci (Landmark edition). 2008;14:1684–707.
15.
Zurück zum Zitat Michaud J, Scott HS, Escher R. AML1 interconnected pathways of leukemogenesis. Cancer Investig. 2003;21(1):105–36. Michaud J, Scott HS, Escher R. AML1 interconnected pathways of leukemogenesis. Cancer Investig. 2003;21(1):105–36.
16.
Zurück zum Zitat Lo Coco F, Pisegna S, Diverio D. The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias. Haematologica. 1997;82(3):364–70.PubMed Lo Coco F, Pisegna S, Diverio D. The AML1 gene: a transcription factor involved in the pathogenesis of myeloid and lymphoid leukemias. Haematologica. 1997;82(3):364–70.PubMed
17.
Zurück zum Zitat Fenske TS, Pengue G, Graubert TA. Dominant negative effects of the AML1/ETO fusion oncoprotein. Cell Cycle. 2005;4(1):33–6.PubMed Fenske TS, Pengue G, Graubert TA. Dominant negative effects of the AML1/ETO fusion oncoprotein. Cell Cycle. 2005;4(1):33–6.PubMed
18.
Zurück zum Zitat Stone RM. Prognostic factors in AML in relation to (ab) normal karyotype. Best Pract Res Clin Haematol. 2009;22(4):523–8.PubMed Stone RM. Prognostic factors in AML in relation to (ab) normal karyotype. Best Pract Res Clin Haematol. 2009;22(4):523–8.PubMed
19.
Zurück zum Zitat Blum W, Marcucci G. New approaches in acute myeloid leukemia. Best Pract Res Clin Haematol. 2008;21(1):29–41.PubMed Blum W, Marcucci G. New approaches in acute myeloid leukemia. Best Pract Res Clin Haematol. 2008;21(1):29–41.PubMed
20.
Zurück zum Zitat Delaunay J, Vey N, Leblanc T, Fenaux P, Rigal-Huguet F, Witz F, et al. Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup. Blood. 2003;102(2):462–9.PubMed Delaunay J, Vey N, Leblanc T, Fenaux P, Rigal-Huguet F, Witz F, et al. Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup. Blood. 2003;102(2):462–9.PubMed
21.
Zurück zum Zitat Clozel T, Renneville A, Venot M, Gardin C, Kelaidi C, Leroux G, et al. Slow relapse in acute myeloid leukemia with inv(16) or t(16;16). Haematologica. 2009;94(10):1466–7.PubMedPubMedCentral Clozel T, Renneville A, Venot M, Gardin C, Kelaidi C, Leroux G, et al. Slow relapse in acute myeloid leukemia with inv(16) or t(16;16). Haematologica. 2009;94(10):1466–7.PubMedPubMedCentral
22.
Zurück zum Zitat Hartl M, Bister K. Oncogenes. In: Hughes SM, editor. Brenner’s encyclopedia of genetics. 2nd ed. San Diego: Academic Press; 2013. p. 164–6. Hartl M, Bister K. Oncogenes. In: Hughes SM, editor. Brenner’s encyclopedia of genetics. 2nd ed. San Diego: Academic Press; 2013. p. 164–6.
23.
Zurück zum Zitat Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P, et al. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. 1996;87(3):1089–96.PubMed Carow CE, Levenstein M, Kaufmann SH, Chen J, Amin S, Rockwell P, et al. Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. 1996;87(3):1089–96.PubMed
24.
Zurück zum Zitat Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber Philipp B, Di Ruscio A, et al. Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia. Cancer Cell. 2013;24(5):575–88.PubMedPubMedCentral Zhang H, Alberich-Jorda M, Amabile G, Yang H, Staber Philipp B, Di Ruscio A, et al. Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia. Cancer Cell. 2013;24(5):575–88.PubMedPubMedCentral
25.
Zurück zum Zitat Butturini A, Gale RP. Oncogenes and leukemia. Leukemia. 1990;4(2):138–60.PubMed Butturini A, Gale RP. Oncogenes and leukemia. Leukemia. 1990;4(2):138–60.PubMed
26.
Zurück zum Zitat Shih L, Huang C, Wang P, Wu J, Lin T, Dunn P, et al. Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia. 2004;18(3):466–75.PubMed Shih L, Huang C, Wang P, Wu J, Lin T, Dunn P, et al. Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia. 2004;18(3):466–75.PubMed
27.
Zurück zum Zitat Shih L-Y, Huang C-F, Wu J-H, Lin T-L, Dunn P, Wang P-N, et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood. 2002;100(7):2387–92.PubMed Shih L-Y, Huang C-F, Wu J-H, Lin T-L, Dunn P, Wang P-N, et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood. 2002;100(7):2387–92.PubMed
28.
Zurück zum Zitat Whitman SP, Ruppert AS, Radmacher MD, Mrózek K, Paschka P, Langer C, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111(3):1552–9.PubMedPubMedCentral Whitman SP, Ruppert AS, Radmacher MD, Mrózek K, Paschka P, Langer C, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111(3):1552–9.PubMedPubMedCentral
29.
Zurück zum Zitat Fröhling S, Scholl C, Gilliland DG, Levine RL. Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol. 2005;23(26):6285–95.PubMed Fröhling S, Scholl C, Gilliland DG, Levine RL. Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol. 2005;23(26):6285–95.PubMed
30.
Zurück zum Zitat Breitenbuecher F, Schnittger S, Grundler R, Markova B, Carius B, Brecht A, et al. Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor. Blood. 2009;113(17):4074–7.PubMed Breitenbuecher F, Schnittger S, Grundler R, Markova B, Carius B, Brecht A, et al. Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor. Blood. 2009;113(17):4074–7.PubMed
31.
Zurück zum Zitat Scholl S, Loncarevic IF, Krause C, Kunert C, Clement JH, Höffken K. Minimal residual disease based on patient specific Flt3-ITD and -ITT mutations in acute myeloid leukemia. Leuk Res. 2005;29(7):849–53.PubMed Scholl S, Loncarevic IF, Krause C, Kunert C, Clement JH, Höffken K. Minimal residual disease based on patient specific Flt3-ITD and -ITT mutations in acute myeloid leukemia. Leuk Res. 2005;29(7):849–53.PubMed
32.
Zurück zum Zitat Stirewalt DL, Willman CL, Radich JP. Quantitative, real-time polymerase chain reactions for FLT3 internal tandem duplications are highly sensitive and specific. Leuk Res. 2001;25(12):1085–8.PubMed Stirewalt DL, Willman CL, Radich JP. Quantitative, real-time polymerase chain reactions for FLT3 internal tandem duplications are highly sensitive and specific. Leuk Res. 2001;25(12):1085–8.PubMed
33.
Zurück zum Zitat Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Am Soc Hematol Educ Program Book. 2013;2013(1):220–6. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Am Soc Hematol Educ Program Book. 2013;2013(1):220–6.
34.
Zurück zum Zitat Nguyen LA, Pandolfi PP, Aikawa Y, Tagata Y, Ohki M, Kitabayashi I. Physical and functional link of the leukemia-associated factors AML1 and PML. Blood. 2005;105(1):292–300.PubMed Nguyen LA, Pandolfi PP, Aikawa Y, Tagata Y, Ohki M, Kitabayashi I. Physical and functional link of the leukemia-associated factors AML1 and PML. Blood. 2005;105(1):292–300.PubMed
35.
Zurück zum Zitat Wang Q, Stacy T, Miller JD, Lewis AF, Gu TL, Huang X, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell. 1996;87(4):697–708.PubMed Wang Q, Stacy T, Miller JD, Lewis AF, Gu TL, Huang X, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell. 1996;87(4):697–708.PubMed
36.
Zurück zum Zitat Cameron ER, Neil JC. The Runx genes: lineage-specific oncogenes and tumor suppressors. Oncogene. 2004;23(24):4308–14.PubMed Cameron ER, Neil JC. The Runx genes: lineage-specific oncogenes and tumor suppressors. Oncogene. 2004;23(24):4308–14.PubMed
37.
Zurück zum Zitat Higuchi M, O’Brien D, Kumaravelu P, Lenny N, Yeoh E-J, Downing JR. Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell. 2002;1(1):63–74.PubMed Higuchi M, O’Brien D, Kumaravelu P, Lenny N, Yeoh E-J, Downing JR. Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell. 2002;1(1):63–74.PubMed
38.
Zurück zum Zitat Tang J-L, Hou H-A, Chen C-Y, Liu C-Y, Chou W-C, Tseng M-H. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood. 2009;114(26):5352–61.PubMed Tang J-L, Hou H-A, Chen C-Y, Liu C-Y, Chou W-C, Tseng M-H. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood. 2009;114(26):5352–61.PubMed
39.
Zurück zum Zitat Al-Baradie R, Yamada K, Hilaire CS, Chan W-M, Andrews C, McIntosh N, et al. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002;71(5):1195–9.PubMedPubMedCentral Al-Baradie R, Yamada K, Hilaire CS, Chan W-M, Andrews C, McIntosh N, et al. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002;71(5):1195–9.PubMedPubMedCentral
40.
Zurück zum Zitat Wang F, Guo Y, Chen Q, Yang Z, Ning N, Zhang Y, et al. Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes. J Hematol Oncol. 2013;6:73.PubMedPubMedCentral Wang F, Guo Y, Chen Q, Yang Z, Ning N, Zhang Y, et al. Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes. J Hematol Oncol. 2013;6:73.PubMedPubMedCentral
41.
Zurück zum Zitat Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.PubMedPubMedCentral Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.PubMedPubMedCentral
42.
Zurück zum Zitat Merup M, Lazarevic V, Nahi H, Andreasson B, Malm C, Nilsson L, et al. Different outcome of allogeneic transplantation in myelofibrosis using conventional or reduced‐intensity conditioning regimens. Br J Haematol. 2006;135(3):367–73.PubMed Merup M, Lazarevic V, Nahi H, Andreasson B, Malm C, Nilsson L, et al. Different outcome of allogeneic transplantation in myelofibrosis using conventional or reduced‐intensity conditioning regimens. Br J Haematol. 2006;135(3):367–73.PubMed
43.
Zurück zum Zitat Yang J, Chai L, Gao C, Fowles TC, Alipio Z, Dang H, et al. SALL4 is a key regulator of survival and apoptosis in human leukemic cells. Blood. 2008;112(3):805–13.PubMedPubMedCentral Yang J, Chai L, Gao C, Fowles TC, Alipio Z, Dang H, et al. SALL4 is a key regulator of survival and apoptosis in human leukemic cells. Blood. 2008;112(3):805–13.PubMedPubMedCentral
44.
Zurück zum Zitat Shuai X, Zhou D, Shen T, Wu Y, Zhang J, Wang X, et al. Overexpression of the novel oncogene SALL4 and activation of the Wnt/β-catenin pathway in myelodysplastic syndromes. Cancer Genet Cytogenet. 2009;194(2):119–24.PubMed Shuai X, Zhou D, Shen T, Wu Y, Zhang J, Wang X, et al. Overexpression of the novel oncogene SALL4 and activation of the Wnt/β-catenin pathway in myelodysplastic syndromes. Cancer Genet Cytogenet. 2009;194(2):119–24.PubMed
45.
Zurück zum Zitat Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, et al. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci. 2007;104(25):10494–9.PubMedPubMedCentral Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, et al. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci. 2007;104(25):10494–9.PubMedPubMedCentral
46.
Zurück zum Zitat Chen Q, Qian J, Lin J, Yang J, Li Y, Wang C, et al. Expression of SALL4 gene in patients with acute and chronic myeloid leukemia. Zhongguo shi yan xue ye xue za zhi/Zhongguo bing li sheng li xue hui. Journal of Experimental Hematology/Chinese Association of Pathophysiology. 2013;21(2):315–9. Chen Q, Qian J, Lin J, Yang J, Li Y, Wang C, et al. Expression of SALL4 gene in patients with acute and chronic myeloid leukemia. Zhongguo shi yan xue ye xue za zhi/Zhongguo bing li sheng li xue hui. Journal of Experimental Hematology/Chinese Association of Pathophysiology. 2013;21(2):315–9.
47.
Zurück zum Zitat Ma J-c, Qian J, Lin J, Qian W, Yang J, Wang C-z, et al. Aberrant hypomethylation of SALL4 gene is associated with intermediate and poor karyotypes in acute myeloid leukemia. Clin Biochem. 2013;46(4):304–7.PubMed Ma J-c, Qian J, Lin J, Qian W, Yang J, Wang C-z, et al. Aberrant hypomethylation of SALL4 gene is associated with intermediate and poor karyotypes in acute myeloid leukemia. Clin Biochem. 2013;46(4):304–7.PubMed
48.
Zurück zum Zitat Jeong H-W, Cui W, Yang Y, Lu J, He J, Li A, et al. SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes. PLoS ONE. 2011;6(4):e18372.PubMedPubMedCentral Jeong H-W, Cui W, Yang Y, Lu J, He J, Li A, et al. SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes. PLoS ONE. 2011;6(4):e18372.PubMedPubMedCentral
49.
Zurück zum Zitat Hinds PW, Weinberg RA. Tumor suppressor genes. Curr Opinion Gen Dev. 1994;4(1):135–41. Hinds PW, Weinberg RA. Tumor suppressor genes. Curr Opinion Gen Dev. 1994;4(1):135–41.
50.
Zurück zum Zitat Osborne C, Wilson P, Tripathy D. Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist. 2004;9(4):361–77.PubMed Osborne C, Wilson P, Tripathy D. Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist. 2004;9(4):361–77.PubMed
51.
Zurück zum Zitat Menke AL, Van der Eb A, Jochemsen A. The Wilms’ tumor 1 gene: oncogene or tumor suppressor gene? Int Rev Cytol. 1998;181:151–212.PubMed Menke AL, Van der Eb A, Jochemsen A. The Wilms’ tumor 1 gene: oncogene or tumor suppressor gene? Int Rev Cytol. 1998;181:151–212.PubMed
52.
Zurück zum Zitat Hosen N, Sonoda Y, Oji Y, Kimura T, Minamiguchi H, Tamaki H, et al. Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol. 2002;116(2):409–20.PubMed Hosen N, Sonoda Y, Oji Y, Kimura T, Minamiguchi H, Tamaki H, et al. Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol. 2002;116(2):409–20.PubMed
53.
Zurück zum Zitat Owen C, Fitzgibbon J, Paschka P. The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia. Hematol Oncol. 2010;28(1):13–9.PubMed Owen C, Fitzgibbon J, Paschka P. The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia. Hematol Oncol. 2010;28(1):13–9.PubMed
54.
Zurück zum Zitat Svensson E, Eriksson H, Gekas C, Olofsson T, Richter J, Gullberg U. DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis. Exp Cell Res. 2005;308(1):211–21.PubMed Svensson E, Eriksson H, Gekas C, Olofsson T, Richter J, Gullberg U. DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis. Exp Cell Res. 2005;308(1):211–21.PubMed
55.
Zurück zum Zitat Huff V. Wilms’ tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer. 2011;11(2):111–21.PubMedPubMedCentral Huff V. Wilms’ tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer. 2011;11(2):111–21.PubMedPubMedCentral
56.
Zurück zum Zitat Summers K, Stevens J, Kakkas I, Smith M, Smith L, Macdougall F, et al. Wilms’ tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML. Leukemia. 2007;21(3):550–1.PubMed Summers K, Stevens J, Kakkas I, Smith M, Smith L, Macdougall F, et al. Wilms’ tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML. Leukemia. 2007;21(3):550–1.PubMed
57.
Zurück zum Zitat Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrózek K, Maharry K, et al. Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol. 2008;26(28):4595–602.PubMedPubMedCentral Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrózek K, Maharry K, et al. Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol. 2008;26(28):4595–602.PubMedPubMedCentral
58.
Zurück zum Zitat Hollink IH, van den Heuvel-Eibrink MM, Zimmermann M, Balgobind BV, Arentsen-Peters ST, Alders M, et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia. Blood. 2009;113(23):5951–60.PubMed Hollink IH, van den Heuvel-Eibrink MM, Zimmermann M, Balgobind BV, Arentsen-Peters ST, Alders M, et al. Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia. Blood. 2009;113(23):5951–60.PubMed
59.
Zurück zum Zitat Ellisen LW, Carlesso N, Cheng T, Scadden DT, Haber DA. The Wilms tumor suppressor WT1 directs stage‐specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J. 2001;20(8):1897–909.PubMedPubMedCentral Ellisen LW, Carlesso N, Cheng T, Scadden DT, Haber DA. The Wilms tumor suppressor WT1 directs stage‐specific quiescence and differentiation of human hematopoietic progenitor cells. EMBO J. 2001;20(8):1897–909.PubMedPubMedCentral
60.
61.
Zurück zum Zitat Sternsdorf T, Grötzinger T, Jensen K, Will H. Nuclear dots: actors on many stages. Immunobiology. 1997;198(1):307–31.PubMed Sternsdorf T, Grötzinger T, Jensen K, Will H. Nuclear dots: actors on many stages. Immunobiology. 1997;198(1):307–31.PubMed
62.
Zurück zum Zitat Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito SI, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature. 2000;406(6792):207–10.PubMed Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito SI, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature. 2000;406(6792):207–10.PubMed
63.
Zurück zum Zitat Salomoni P, Pandolfi PP. The role of PML in tumor suppression. Cell. 2002;108(2):165–70.PubMed Salomoni P, Pandolfi PP. The role of PML in tumor suppression. Cell. 2002;108(2):165–70.PubMed
64.
Zurück zum Zitat Jensen K, Shiels C, Freemont PS. PML protein isoforms and the RBCC/TRIM motif. Oncogene. 2001;20(49):7223–33.PubMed Jensen K, Shiels C, Freemont PS. PML protein isoforms and the RBCC/TRIM motif. Oncogene. 2001;20(49):7223–33.PubMed
65.
Zurück zum Zitat Gamell C, Jan Paul P, Haupt Y, Haupt S. PML tumour suppression and beyond: therapeutic implications. FEBS Lett. 2014;588(16):2653–62.PubMed Gamell C, Jan Paul P, Haupt Y, Haupt S. PML tumour suppression and beyond: therapeutic implications. FEBS Lett. 2014;588(16):2653–62.PubMed
66.
Zurück zum Zitat Bernardi R, Pandolfi PP. Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene. 2003;22(56):9048–57.PubMed Bernardi R, Pandolfi PP. Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene. 2003;22(56):9048–57.PubMed
67.
Zurück zum Zitat Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, et al. ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood. 2006;107(8):3330–8.PubMedPubMedCentral Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, et al. ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood. 2006;107(8):3330–8.PubMedPubMedCentral
68.
Zurück zum Zitat Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Petti MC, et al. Autologous bone marrow transplantation for acute promyelocytic leukemia in second remission: prognostic relevance of pretransplant minimal residual disease assessment by reverse-transcription polymerase chain reaction of the PML/RARα fusion gene. Blood. 1997;90(3):1321–5.PubMed Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Petti MC, et al. Autologous bone marrow transplantation for acute promyelocytic leukemia in second remission: prognostic relevance of pretransplant minimal residual disease assessment by reverse-transcription polymerase chain reaction of the PML/RARα fusion gene. Blood. 1997;90(3):1321–5.PubMed
69.
Zurück zum Zitat Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113(25):6403–10.PubMedPubMedCentral Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113(25):6403–10.PubMedPubMedCentral
70.
Zurück zum Zitat Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7.PubMedPubMedCentral Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7.PubMedPubMedCentral
71.
Zurück zum Zitat Delhommeau F, Dupont S, Valle VD, James C, Trannoy S, Masse A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.PubMed Delhommeau F, Dupont S, Valle VD, James C, Trannoy S, Masse A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.PubMed
72.
Zurück zum Zitat Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11–24.PubMedPubMedCentral Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell. 2011;20(1):11–24.PubMedPubMedCentral
73.
Zurück zum Zitat Chou W-C, Chou S-C, Liu C-Y, Chen C-Y, Hou H-A, Kuo Y-Y, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood. 2011;118(14):3803–10.PubMed Chou W-C, Chou S-C, Liu C-Y, Chen C-Y, Hou H-A, Kuo Y-Y, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood. 2011;118(14):3803–10.PubMed
74.
Zurück zum Zitat Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67.PubMedPubMedCentral Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67.PubMedPubMedCentral
75.
Zurück zum Zitat Weissmann S, Alpermann T, Grossmann V, Kowarsch A, Nadarajah N, Eder C, et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia. 2012;26(5):934–42.PubMed Weissmann S, Alpermann T, Grossmann V, Kowarsch A, Nadarajah N, Eder C, et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia. 2012;26(5):934–42.PubMed
76.
Zurück zum Zitat Kosmider O, Gelsi-Boyer V, Cheok M, Grabar S, Della-Valle V, Picard F, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114(15):3285–91.PubMed Kosmider O, Gelsi-Boyer V, Cheok M, Grabar S, Della-Valle V, Picard F, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114(15):3285–91.PubMed
77.
Zurück zum Zitat Lorsbach R, Moore J, Mathew S, Raimondi S, Mukatira S, Downing J. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t (10; 11)(q22; q23). Leukemia. 2003;17(3):637–41.PubMed Lorsbach R, Moore J, Mathew S, Raimondi S, Mukatira S, Downing J. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t (10; 11)(q22; q23). Leukemia. 2003;17(3):637–41.PubMed
78.
Zurück zum Zitat Estey EH. Acute myeloid leukemia: 2013 update on risk‐stratification and management. Am J Hematol. 2013;88(4):317–27. Estey EH. Acute myeloid leukemia: 2013 update on risk‐stratification and management. Am J Hematol. 2013;88(4):317–27.
79.
Zurück zum Zitat Zheng J, Wang X, Hu Y, Yang J, Liu J, He Y, et al. A correlation study of immunophenotypic, cytogenetic, and clinical features of 180 AML patients in China. Cytometry B Clin Cytom. 2008;74(1):25–9.PubMed Zheng J, Wang X, Hu Y, Yang J, Liu J, He Y, et al. A correlation study of immunophenotypic, cytogenetic, and clinical features of 180 AML patients in China. Cytometry B Clin Cytom. 2008;74(1):25–9.PubMed
80.
Zurück zum Zitat Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93(9):3074–80.PubMed Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93(9):3074–80.PubMed
82.
Zurück zum Zitat Paschka P, Marcucci G, Ruppert AS, Mrózek K, Chen H, Kittles RA, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv (16) and t (8; 21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24(24):3904–11.PubMed Paschka P, Marcucci G, Ruppert AS, Mrózek K, Chen H, Kittles RA, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv (16) and t (8; 21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24(24):3904–11.PubMed
83.
Zurück zum Zitat Preudhomme C, Sagot C, Boissel N, Cayuela J-M, Tigaud I, de Botton S, et al. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002;100(8):2717–23.PubMed Preudhomme C, Sagot C, Boissel N, Cayuela J-M, Tigaud I, de Botton S, et al. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002;100(8):2717–23.PubMed
84.
Zurück zum Zitat Liang D-C, Liu H-C, Yang C-P, Jaing T-H, Hung I-J, Yeh T-C, et al. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A. Blood. 2013;121(15):2988–95.PubMed Liang D-C, Liu H-C, Yang C-P, Jaing T-H, Hung I-J, Yeh T-C, et al. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A. Blood. 2013;121(15):2988–95.PubMed
85.
Zurück zum Zitat Gao C, Dimitrov T, Yong KJ, Tatetsu H, Jeong H-W, Luo HR, et al. Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood. 2013;121(8):1413–21.PubMedPubMedCentral Gao C, Dimitrov T, Yong KJ, Tatetsu H, Jeong H-W, Luo HR, et al. Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood. 2013;121(8):1413–21.PubMedPubMedCentral
86.
Zurück zum Zitat Chong PS, Zhou J, Cheong L-L, Liu S-C, Qian J, Guo T, et al. LEO1 is regulated by PRL-3 and mediates its oncogenic properties in acute myelogenous leukemia. Cancer Res. 2014;74(11):3043–53.PubMed Chong PS, Zhou J, Cheong L-L, Liu S-C, Qian J, Guo T, et al. LEO1 is regulated by PRL-3 and mediates its oncogenic properties in acute myelogenous leukemia. Cancer Res. 2014;74(11):3043–53.PubMed
87.
Zurück zum Zitat Park JE, Yuen HF, Zhou JB, Al‐aidaroos AQO, Guo K, Valk PJ, et al. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia. EMBO Mol Med. 2013;5(9):1351–66.PubMedPubMedCentral Park JE, Yuen HF, Zhou JB, Al‐aidaroos AQO, Guo K, Valk PJ, et al. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia. EMBO Mol Med. 2013;5(9):1351–66.PubMedPubMedCentral
88.
Zurück zum Zitat Qu S, Liu B, Guo X, Shi H, Zhou M, Li L, et al. Independent oncogenic and therapeutic significance of phosphatase PRL-3 in FLT3-ITD–negative acute myeloid leukemia. Cancer. 2014;120(14):2130–41.PubMed Qu S, Liu B, Guo X, Shi H, Zhou M, Li L, et al. Independent oncogenic and therapeutic significance of phosphatase PRL-3 in FLT3-ITD–negative acute myeloid leukemia. Cancer. 2014;120(14):2130–41.PubMed
89.
Zurück zum Zitat Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol. 1999;105(4):894–900.PubMed Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol. 1999;105(4):894–900.PubMed
90.
Zurück zum Zitat Liu D, Jiang H, Qin Y-Z, Xu L-P, Jiang Q, Zhang X-H, et al. KIT mutation versus MRD, which is more important to predict relapse of acute myeloid leukemia with t (8; 21)? Blood. 2013;122(21):1309–9. Liu D, Jiang H, Qin Y-Z, Xu L-P, Jiang Q, Zhang X-H, et al. KIT mutation versus MRD, which is more important to predict relapse of acute myeloid leukemia with t (8; 21)? Blood. 2013;122(21):1309–9.
91.
Zurück zum Zitat Naoe T, Kiyoi H. Normal and oncogenic FLT3. Cell Mol Life Sci. 2004;61(23):2932–8.PubMed Naoe T, Kiyoi H. Normal and oncogenic FLT3. Cell Mol Life Sci. 2004;61(23):2932–8.PubMed
92.
Zurück zum Zitat Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100(1):59–66.PubMed Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002;100(1):59–66.PubMed
93.
Zurück zum Zitat Kainz B, Heintel D, Marculescu R, Schwarzinger I, Sperr W, Le T, et al. Variable prognostic value of FLT3 internal tandem duplications in patients with de novo AML and a normal karyotype, t (15; 17), t (8; 21) or inv (16). Hematol J. 2002;3(6):283–9.PubMed Kainz B, Heintel D, Marculescu R, Schwarzinger I, Sperr W, Le T, et al. Variable prognostic value of FLT3 internal tandem duplications in patients with de novo AML and a normal karyotype, t (15; 17), t (8; 21) or inv (16). Hematol J. 2002;3(6):283–9.PubMed
94.
Zurück zum Zitat Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98(6):1752–9.PubMed Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98(6):1752–9.PubMed
95.
Zurück zum Zitat Chan IT, Gilliland DG. Oncogenic K-ras in mouse models of myeloproliferative disease and acute myeloid leukemia. Cell Cycle. 2004;3(5):534–5. Chan IT, Gilliland DG. Oncogenic K-ras in mouse models of myeloproliferative disease and acute myeloid leukemia. Cell Cycle. 2004;3(5):534–5.
96.
Zurück zum Zitat Neubauer A, Dodge R, George S, Davey F, Silver R, Schiffer C, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994;83(6):1603–11.PubMed Neubauer A, Dodge R, George S, Davey F, Silver R, Schiffer C, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994;83(6):1603–11.PubMed
97.
Zurück zum Zitat Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman CL, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97(11):3589–95.PubMed Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman CL, et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001;97(11):3589–95.PubMed
98.
Zurück zum Zitat Lutterbach B, Hiebert S. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene. 2000;245(2):223–35.PubMed Lutterbach B, Hiebert S. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene. 2000;245(2):223–35.PubMed
99.
Zurück zum Zitat Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996;84(2):321–30.PubMed Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell. 1996;84(2):321–30.PubMed
100.
Zurück zum Zitat Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, et al. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest. 2013;123(9):3876.PubMedPubMedCentral Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, et al. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest. 2013;123(9):3876.PubMedPubMedCentral
101.
Zurück zum Zitat Mendler JH, Maharry K, Radmacher MD, Mrózek K, Becker H, Metzeler KH, et al. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures. J Clin Oncol. 2012;30(25):3109–18.PubMedPubMedCentral Mendler JH, Maharry K, Radmacher MD, Mrózek K, Becker H, Metzeler KH, et al. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures. J Clin Oncol. 2012;30(25):3109–18.PubMedPubMedCentral
102.
Zurück zum Zitat Schessl C, Rawat VPS, Cusan M, Deshpande A, Kohl TM, Rosten PM, et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005;115(8):2159–68.PubMedPubMedCentral Schessl C, Rawat VPS, Cusan M, Deshpande A, Kohl TM, Rosten PM, et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005;115(8):2159–68.PubMedPubMedCentral
103.
Zurück zum Zitat Wieser R. The oncogene and developmental regulator EVI1: Expression, biochemical properties, and biological functions. Gene. 2007;396(2):346–57.PubMed Wieser R. The oncogene and developmental regulator EVI1: Expression, biochemical properties, and biological functions. Gene. 2007;396(2):346–57.PubMed
104.
Zurück zum Zitat Nucifora G. The EVI1 gene in myeloid leukemia. Leukemia. 1997;11(12):2022–31.PubMed Nucifora G. The EVI1 gene in myeloid leukemia. Leukemia. 1997;11(12):2022–31.PubMed
105.
Zurück zum Zitat Lennon PA, Abruzzo LV, Medeiros LJ, Cromwell C, Zhang X, Yin CC, et al. Aberrant EVI1 expression in acute myeloid leukemias associated with the t (3; 8)(q26; q24). Cancer Genet Cytogenet. 2007;177(1):37–42.PubMed Lennon PA, Abruzzo LV, Medeiros LJ, Cromwell C, Zhang X, Yin CC, et al. Aberrant EVI1 expression in acute myeloid leukemias associated with the t (3; 8)(q26; q24). Cancer Genet Cytogenet. 2007;177(1):37–42.PubMed
106.
Zurück zum Zitat Gröschel S, Lugthart S, Schlenk RF, Valk PJM, Eiwen K, Goudswaard C, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28(12):2101–7.PubMed Gröschel S, Lugthart S, Schlenk RF, Valk PJM, Eiwen K, Goudswaard C, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28(12):2101–7.PubMed
107.
Zurück zum Zitat Shearer BM, Knudson RA, Flynn HC, Ketterling RP. Development of a D-FISH method to detect DEK/CAN fusion resulting from t(6;9)(p23;q34) in patients with acute myelogenous leukemia. Leukemia. 2005;19(1):126–31.PubMed Shearer BM, Knudson RA, Flynn HC, Ketterling RP. Development of a D-FISH method to detect DEK/CAN fusion resulting from t(6;9)(p23;q34) in patients with acute myelogenous leukemia. Leukemia. 2005;19(1):126–31.PubMed
108.
Zurück zum Zitat Logan GE, Mor-Vaknin N, Braunschweig T, Jost E, Schmidt PV, Markovitz DM, et al. DEK oncogene expression during normal hematopoiesis and in acute myeloid leukemia (AML). Blood Cell Mol Dis. 2015;54(1):123–31. Logan GE, Mor-Vaknin N, Braunschweig T, Jost E, Schmidt PV, Markovitz DM, et al. DEK oncogene expression during normal hematopoiesis and in acute myeloid leukemia (AML). Blood Cell Mol Dis. 2015;54(1):123–31.
109.
Zurück zum Zitat Sandahl JD, Coenen EA, Forestier E, Harbott J, Johansson B, Kerndrup G, et al. t (6; 9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica. 2014;99(5):865–72.PubMedPubMedCentral Sandahl JD, Coenen EA, Forestier E, Harbott J, Johansson B, Kerndrup G, et al. t (6; 9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica. 2014;99(5):865–72.PubMedPubMedCentral
110.
Zurück zum Zitat Heuser M, Beutel G, Krauter J, Döhner K, von Neuhoff N, Schlegelberger B, et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood. 2006;108(12):3898–905.PubMed Heuser M, Beutel G, Krauter J, Döhner K, von Neuhoff N, Schlegelberger B, et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood. 2006;108(12):3898–905.PubMed
112.
Zurück zum Zitat Liu T, Jankovic D, Brault L, Ehret S, Baty F, Stavropoulou V, et al. Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia. Leukemia. 2010;24(3):601–12.PubMed Liu T, Jankovic D, Brault L, Ehret S, Baty F, Stavropoulou V, et al. Functional characterization of high levels of meningioma 1 as collaborating oncogene in acute leukemia. Leukemia. 2010;24(3):601–12.PubMed
113.
Zurück zum Zitat Shankar DB, Cheng JC, Kinjo K, Federman N, Moore TB, Gill A, et al. The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia. Cancer Cell. 2005;7(4):351–62.PubMed Shankar DB, Cheng JC, Kinjo K, Federman N, Moore TB, Gill A, et al. The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia. Cancer Cell. 2005;7(4):351–62.PubMed
114.
Zurück zum Zitat Siu Y-T, Jin D-Y. CREB—a real culprit in oncogenesis. FEBS J. 2007;274(13):3224–32.PubMed Siu Y-T, Jin D-Y. CREB—a real culprit in oncogenesis. FEBS J. 2007;274(13):3224–32.PubMed
115.
Zurück zum Zitat Kinjo K, Sandoval S, Sakamoto KM, Shankar DB. The role of CREB as a proto-oncogene in hematopoiesis. Cell Cycle. 2005;4(9):1134–5.PubMed Kinjo K, Sandoval S, Sakamoto KM, Shankar DB. The role of CREB as a proto-oncogene in hematopoiesis. Cell Cycle. 2005;4(9):1134–5.PubMed
116.
Zurück zum Zitat Ho PA, Alonzo TA, Kopecky KJ, Miller KL, Kuhn J, Zeng R, et al. Molecular alterations of the IDH1 gene in AML: a Children’s Oncology Group and Southwest Oncology Group study. Leukemia. 2010;24(5):909–13.PubMedPubMedCentral Ho PA, Alonzo TA, Kopecky KJ, Miller KL, Kuhn J, Zeng R, et al. Molecular alterations of the IDH1 gene in AML: a Children’s Oncology Group and Southwest Oncology Group study. Leukemia. 2010;24(5):909–13.PubMedPubMedCentral
117.
Zurück zum Zitat Chou W-C, Huang H-H, Hou H-A, Chen C-Y, Tang J-L, Yao M, et al. Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood. 2010;116(20):4086–94.PubMed Chou W-C, Huang H-H, Hou H-A, Chen C-Y, Tang J-L, Yao M, et al. Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood. 2010;116(20):4086–94.PubMed
118.
Zurück zum Zitat Metzeler KH, Becker H, Maharry K, Radmacher MD, Kohlschmidt J, Mrózek K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011;118(26):6920–9.PubMedPubMedCentral Metzeler KH, Becker H, Maharry K, Radmacher MD, Kohlschmidt J, Mrózek K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011;118(26):6920–9.PubMedPubMedCentral
119.
Zurück zum Zitat Metzeler KH, Maharry K, Radmacher MD, Mrózek K, Margeson D, Becker H, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2011;29(10):1373–81.PubMedPubMedCentral Metzeler KH, Maharry K, Radmacher MD, Mrózek K, Margeson D, Becker H, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2011;29(10):1373–81.PubMedPubMedCentral
120.
Zurück zum Zitat Nakajima H, Kunimoto H. TET2 as an epigenetic master regulator for normal and malignant hematopoiesis. Cancer Sci. 2014;105(9):1093–9.PubMedPubMedCentral Nakajima H, Kunimoto H. TET2 as an epigenetic master regulator for normal and malignant hematopoiesis. Cancer Sci. 2014;105(9):1093–9.PubMedPubMedCentral
121.
Zurück zum Zitat Hou H-A, Kuo Y-Y, Liu C-Y, Chou W-C, Lee MC, Chen C-Y, et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood. 2012;119(2):559–68.PubMed Hou H-A, Kuo Y-Y, Liu C-Y, Chou W-C, Lee MC, Chen C-Y, et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood. 2012;119(2):559–68.PubMed
122.
Zurück zum Zitat Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33.PubMedPubMedCentral Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33.PubMedPubMedCentral
123.
Zurück zum Zitat Shivarov V, Gueorguieva R, Stoimenov A, Tiu R. DNMT3A mutation is a poor prognosis biomarker in AML: results of a meta-analysis of 4500 AML patients. Leuk Res. 2013;37(11):1445–50.PubMed Shivarov V, Gueorguieva R, Stoimenov A, Tiu R. DNMT3A mutation is a poor prognosis biomarker in AML: results of a meta-analysis of 4500 AML patients. Leuk Res. 2013;37(11):1445–50.PubMed
124.
Zurück zum Zitat King-Underwood L, Renshaw J, Pritchard-Jones K. Mutations in the Wilms’ tumor gene WT1 in leukemias. Blood. 1996;87(6):2171–9.PubMed King-Underwood L, Renshaw J, Pritchard-Jones K. Mutations in the Wilms’ tumor gene WT1 in leukemias. Blood. 1996;87(6):2171–9.PubMed
125.
Zurück zum Zitat Yang L, Han Y, Saiz FS, Minden M. A tumor suppressor and oncogene: the WT1 story. Leukemia. 2007;21(5):868–76.PubMed Yang L, Han Y, Saiz FS, Minden M. A tumor suppressor and oncogene: the WT1 story. Leukemia. 2007;21(5):868–76.PubMed
126.
Zurück zum Zitat Trka J, Kalinova M, Hrusak O, Zuna J, Krejci O, Madzo J, et al. Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia. 2002;16(7):1381–9.PubMed Trka J, Kalinova M, Hrusak O, Zuna J, Krejci O, Madzo J, et al. Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia. 2002;16(7):1381–9.PubMed
127.
Zurück zum Zitat Bally C, Adès L, Renneville A, Sebert M, Eclache V, Preudhomme C, et al. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine. Leuk Res. 2014;38(7):751–5.PubMed Bally C, Adès L, Renneville A, Sebert M, Eclache V, Preudhomme C, et al. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine. Leuk Res. 2014;38(7):751–5.PubMed
128.
Zurück zum Zitat Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol. 2001;19(5):1405–13.PubMed Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol. 2001;19(5):1405–13.PubMed
129.
Zurück zum Zitat Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, et al. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood. 2005;106(9):3150–9.PubMedPubMedCentral Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, et al. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood. 2005;106(9):3150–9.PubMedPubMedCentral
130.
Zurück zum Zitat Zhao Z, Zuber J, Diaz-Flores E, Lintault L, Kogan SC, Shannon K, et al. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal. Genes Dev. 2010;24(13):1389–402.PubMedPubMedCentral Zhao Z, Zuber J, Diaz-Flores E, Lintault L, Kogan SC, Shannon K, et al. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal. Genes Dev. 2010;24(13):1389–402.PubMedPubMedCentral
131.
Zurück zum Zitat Puccetti E, Ruthardt M. Acute promyelocytic leukemia: PML//RAR[alpha] and the leukemic stem cell. Leukemia. 2004;18(7):1169–75.PubMed Puccetti E, Ruthardt M. Acute promyelocytic leukemia: PML//RAR[alpha] and the leukemic stem cell. Leukemia. 2004;18(7):1169–75.PubMed
132.
Zurück zum Zitat Wen X-M, Lin J, Yang J, Yao D-M, Deng Z-Q, Tang C-Y, et al. Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD. Int J Clin Exp Pathol. 2014;7(10):6832.PubMedPubMedCentral Wen X-M, Lin J, Yang J, Yao D-M, Deng Z-Q, Tang C-Y, et al. Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD. Int J Clin Exp Pathol. 2014;7(10):6832.PubMedPubMedCentral
133.
Zurück zum Zitat Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113(26):6558–66.PubMedPubMedCentral Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113(26):6558–66.PubMedPubMedCentral
134.
Zurück zum Zitat Fasan A, Alpermann T, Haferlach C, Grossmann V, Roller A, Kohlmann A, et al. Frequency and prognostic impact of CEBPA proximal, distal and core promoter methylation in normal karyotype AML: a study on 623 cases. PLoS One. 2013;8(2):e54365.PubMedPubMedCentral Fasan A, Alpermann T, Haferlach C, Grossmann V, Roller A, Kohlmann A, et al. Frequency and prognostic impact of CEBPA proximal, distal and core promoter methylation in normal karyotype AML: a study on 623 cases. PLoS One. 2013;8(2):e54365.PubMedPubMedCentral
135.
Zurück zum Zitat Fuchs O. Growth-inhibiting activity of transcription factor C/EBPalpha, its role in haematopoiesis and its tumour suppressor or oncogenic properties in leukaemias. Folia Biol. 2006;53(3):97–108. Fuchs O. Growth-inhibiting activity of transcription factor C/EBPalpha, its role in haematopoiesis and its tumour suppressor or oncogenic properties in leukaemias. Folia Biol. 2006;53(3):97–108.
136.
Zurück zum Zitat Agrawal S, Hofmann W-K, Tidow N, Ehrich M, van den Boom D, Koschmieder S, et al. The C/EBPδ tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood. 2007;109(9):3895–905.PubMed Agrawal S, Hofmann W-K, Tidow N, Ehrich M, van den Boom D, Koschmieder S, et al. The C/EBPδ tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood. 2007;109(9):3895–905.PubMed
Metadaten
Titel
Significance of oncogenes and tumor suppressor genes in AML prognosis
Publikationsdatum
14.05.2016
Erschienen in
Tumor Biology / Ausgabe 8/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5067-1

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