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Erschienen in: Annals of Hematology 6/2013

01.06.2013 | Original Article

Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization

verfasst von: Sandra Heesch, Martin Neumann, Stefan Schwartz, Isabelle Bartram, Cornelia Schlee, Thomas Burmeister, Matthias Hänel, Arnold Ganser, Michael Heuser, Clemens-Martin Wendtner, Wolfgang E. Berdel, Nicola Gökbuget, Dieter Hoelzer, Wolf-Karsten Hofmann, Eckhard Thiel, Claudia D. Baldus

Erschienen in: Annals of Hematology | Ausgabe 6/2013

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Abstract

Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.
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Literatur
1.
Zurück zum Zitat Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, Van't Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786PubMed Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, Van't Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786PubMed
2.
Zurück zum Zitat Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, Ludwig WD, Matutes E, Orfao A, Sperling C, Van't Veer MB (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92:596–599PubMed Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, Ludwig WD, Matutes E, Orfao A, Sperling C, Van't Veer MB (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92:596–599PubMed
3.
Zurück zum Zitat Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951. doi:10.1182/blood-2009-03-209262 PubMedCrossRef Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951. doi:10.​1182/​blood-2009-03-209262 PubMedCrossRef
4.
Zurück zum Zitat Borowitz MJ, Béné M-C, Harris NL, Porwit A, Matutes E (2009) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. WHO Classification of Tumours, Volume 2, Chapter 7: 150 pp Borowitz MJ, Béné M-C, Harris NL, Porwit A, Matutes E (2009) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. WHO Classification of Tumours, Volume 2, Chapter 7: 150 pp
5.
6.
Zurück zum Zitat Zhang Y, Wu D, Sun A, Qiu H, He G, Jin Z, Tang X, Miao M, Fu Z, Han Y (2011) Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series. Acta Haematol 125:210–218. doi:10.1159/000322594 PubMedCrossRef Zhang Y, Wu D, Sun A, Qiu H, He G, Jin Z, Tang X, Miao M, Fu Z, Han Y (2011) Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series. Acta Haematol 125:210–218. doi:10.​1159/​000322594 PubMedCrossRef
7.
Zurück zum Zitat Matutes E, Pickl WF, Van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117. doi:10.1182/blood-2010-10-314682 Matutes E, Pickl WF, Van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117. doi:10.​1182/​blood-2010-10-314682
8.
Zurück zum Zitat Legrand O, Perrot JY, Simonin G, Baudard M, Cadiou M, Blanc C, Ramond S, Viguie F, Marie JP, Zittoun R (1998) Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 100:147–155PubMedCrossRef Legrand O, Perrot JY, Simonin G, Baudard M, Cadiou M, Blanc C, Ramond S, Viguie F, Marie JP, Zittoun R (1998) Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 100:147–155PubMedCrossRef
9.
Zurück zum Zitat Killick S, Matutes E, Powles RL, Hamblin M, Swansbury J, Treleaven JG, Zomas A, Atra A, Catovsky D (1999) Outcome of biphenotypic acute leukemia. Haematologica 84:699–706PubMed Killick S, Matutes E, Powles RL, Hamblin M, Swansbury J, Treleaven JG, Zomas A, Atra A, Catovsky D (1999) Outcome of biphenotypic acute leukemia. Haematologica 84:699–706PubMed
10.
Zurück zum Zitat Rubio MT, Dhedin N, Boucheix C, Bourhis JH, Reman O, Boiron JM, Gallo JH, Lheritier V, Thomas X, Fiere D, Vernant JP (2003) Adult T-biphenotypic acute leukaemia: clinical and biological features and outcome. Br J Haematol 123:842–849PubMedCrossRef Rubio MT, Dhedin N, Boucheix C, Bourhis JH, Reman O, Boiron JM, Gallo JH, Lheritier V, Thomas X, Fiere D, Vernant JP (2003) Adult T-biphenotypic acute leukaemia: clinical and biological features and outcome. Br J Haematol 123:842–849PubMedCrossRef
11.
Zurück zum Zitat Tiribelli M, Damiani D, Masolini P, Candoni A, Calistri E, Fanin R (2004) Biological and clinical features of T-biphenotypic acute leukaemia: report from a single centre. Br J Haematol 125:814–815PubMedCrossRef Tiribelli M, Damiani D, Masolini P, Candoni A, Calistri E, Fanin R (2004) Biological and clinical features of T-biphenotypic acute leukaemia: report from a single centre. Br J Haematol 125:814–815PubMedCrossRef
12.
Zurück zum Zitat Aribi A, Bueso-Ramos C, Estey E, Estrov Z, O'Brien S, Giles F, Faderl S, Thomas D, Kebriaei P, Garcia-Manero G, Pierce S, Cortes J, Kantarjian H, Ravandi F (2007) Biphenotypic acute leukaemia: a case series. Br J Haematol 138:213–216PubMedCrossRef Aribi A, Bueso-Ramos C, Estey E, Estrov Z, O'Brien S, Giles F, Faderl S, Thomas D, Kebriaei P, Garcia-Manero G, Pierce S, Cortes J, Kantarjian H, Ravandi F (2007) Biphenotypic acute leukaemia: a case series. Br J Haematol 138:213–216PubMedCrossRef
13.
Zurück zum Zitat Xu XQ, Wang JM, Lu SQ, Chen L, Yang JM, Zhang WP, Song XM, Hou J, Ni X, Qiu HY (2009) Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population. Haematologica 94:919–927. doi:10.3324/haematol.2008.003202 PubMedCrossRef Xu XQ, Wang JM, Lu SQ, Chen L, Yang JM, Zhang WP, Song XM, Hou J, Ni X, Qiu HY (2009) Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population. Haematologica 94:919–927. doi:10.​3324/​haematol.​2008.​003202 PubMedCrossRef
15.
Zurück zum Zitat Owaidah TM, Al BA, Iqbal MA, Elkum N, Roberts GT (2006) Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia 20:620–626PubMedCrossRef Owaidah TM, Al BA, Iqbal MA, Elkum N, Roberts GT (2006) Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia 20:620–626PubMedCrossRef
16.
Zurück zum Zitat Lee JH, Min YH, Chung CW, Kim BK, Yoon HJ, Jo DY, Shin HJ, Bang SM, Won JH, Zang DY, Kim HJ, Chi HS, Lee KH, Cheong JW, Kim JS, Kim SH, Park S, Park SY, Chung JS, Lee JH, Park CJ (2008) Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma 49:700–709. doi:10.1080/10428190701843247 PubMedCrossRef Lee JH, Min YH, Chung CW, Kim BK, Yoon HJ, Jo DY, Shin HJ, Bang SM, Won JH, Zang DY, Kim HJ, Chi HS, Lee KH, Cheong JW, Kim JS, Kim SH, Park S, Park SY, Chung JS, Lee JH, Park CJ (2008) Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma 49:700–709. doi:10.​1080/​1042819070184324​7 PubMedCrossRef
17.
Zurück zum Zitat Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, Behm FG, Campana D, Razzouk BI, Ribeiro RC, Downing JR, Pui CH (2009) Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood 113:5083–5089. doi:10.1182/blood-2008-10-187351 PubMedCrossRef Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, Behm FG, Campana D, Razzouk BI, Ribeiro RC, Downing JR, Pui CH (2009) Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood 113:5083–5089. doi:10.​1182/​blood-2008-10-187351 PubMedCrossRef
18.
Zurück zum Zitat Brito-Babapulle F, Pullon H, Layton DM, Etches A, Huxtable A, Mangi M, Bellingham AJ, Mufti GJ (1990) Clinicopathological features of acute undifferentiated leukaemia with a stem cell phenotype. Br J Haematol 76:210–214PubMedCrossRef Brito-Babapulle F, Pullon H, Layton DM, Etches A, Huxtable A, Mangi M, Bellingham AJ, Mufti GJ (1990) Clinicopathological features of acute undifferentiated leukaemia with a stem cell phenotype. Br J Haematol 76:210–214PubMedCrossRef
19.
Zurück zum Zitat Bassan R, Biondi A, Benvestito S, Tini ML, Abbate M, Viero P, Barbui T, Rambaldi A (1992) Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of molecular lineage commitment and association with poor prognostic features. Cancer 69:396–404PubMedCrossRef Bassan R, Biondi A, Benvestito S, Tini ML, Abbate M, Viero P, Barbui T, Rambaldi A (1992) Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of molecular lineage commitment and association with poor prognostic features. Cancer 69:396–404PubMedCrossRef
20.
Zurück zum Zitat Cuneo A, Ferrant A, Michaux JL, Bosly A, Chatelain B, Stul M, Dal CP, Dierlamm J, Cassiman JJ, Hossfeld DK, Castoldi G, Van den Berghe H (1996) Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases. Cancer Genet Cytogenet 92:31–36PubMedCrossRef Cuneo A, Ferrant A, Michaux JL, Bosly A, Chatelain B, Stul M, Dal CP, Dierlamm J, Cassiman JJ, Hossfeld DK, Castoldi G, Van den Berghe H (1996) Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases. Cancer Genet Cytogenet 92:31–36PubMedCrossRef
21.
Zurück zum Zitat Heesch S, Goekbuget N, Stroux A, Tanchez JO, Schlee C, Burmeister T, Schwartz S, Blau O, Keilholz U, Busse A, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (2010) Prognostic implications of mutations and expression of the Wilms tumor 1 (WT1) gene in adult acute T-lymphoblastic leukemia. Haematologica 95:942–949. doi:10.3324/haematol.2009.016386 PubMedCrossRef Heesch S, Goekbuget N, Stroux A, Tanchez JO, Schlee C, Burmeister T, Schwartz S, Blau O, Keilholz U, Busse A, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (2010) Prognostic implications of mutations and expression of the Wilms tumor 1 (WT1) gene in adult acute T-lymphoblastic leukemia. Haematologica 95:942–949. doi:10.​3324/​haematol.​2009.​016386 PubMedCrossRef
22.
Zurück zum Zitat Heesch S, Schlee C, Neumann M, Stroux A, Kuhnl A, Schwartz S, Haferlach T, Goekbuget N, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (2010) BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia. Leukemia 24:1429–1436. doi:10.1038/leu.2010.130 PubMedCrossRef Heesch S, Schlee C, Neumann M, Stroux A, Kuhnl A, Schwartz S, Haferlach T, Goekbuget N, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (2010) BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia. Leukemia 24:1429–1436. doi:10.​1038/​leu.​2010.​130 PubMedCrossRef
23.
Zurück zum Zitat Kuhnl A, Gokbuget N, Stroux A, Burmeister T, Neumann M, Heesch S, Haferlach T, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2010) High BAALC expression predicts chemoresistance in adult B-precursor acute lymphoblastic leukemia. Blood 115:3737–3744. doi:10.1182/blood-2009-09-241943 PubMedCrossRef Kuhnl A, Gokbuget N, Stroux A, Burmeister T, Neumann M, Heesch S, Haferlach T, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2010) High BAALC expression predicts chemoresistance in adult B-precursor acute lymphoblastic leukemia. Blood 115:3737–3744. doi:10.​1182/​blood-2009-09-241943 PubMedCrossRef
24.
Zurück zum Zitat Kuhnl A, Kaiser M, Neumann M, Fransecky L, Heesch S, Radmacher M, Marcucci G, Bloomfield CD, Hofmann WK, Thiel E, Baldus CD (2011) High expression of IGFBP2 is associated with chemoresistance in adult acute myeloid leukemia. Leuk Res 35:1585–1590. doi:10.1016/j.leukres.2011.08.006 PubMedCrossRef Kuhnl A, Kaiser M, Neumann M, Fransecky L, Heesch S, Radmacher M, Marcucci G, Bloomfield CD, Hofmann WK, Thiel E, Baldus CD (2011) High expression of IGFBP2 is associated with chemoresistance in adult acute myeloid leukemia. Leuk Res 35:1585–1590. doi:10.​1016/​j.​leukres.​2011.​08.​006 PubMedCrossRef
25.
Zurück zum Zitat Schwartz S, Rieder H, Schlager B, Burmeister T, Fischer L, Thiel E (2003) Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(−)/CD24(−)/CD65s(+)/CD15(+) B-cell phenotype. Leukemia 17:1589–1595PubMedCrossRef Schwartz S, Rieder H, Schlager B, Burmeister T, Fischer L, Thiel E (2003) Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(−)/CD24(−)/CD65s(+)/CD15(+) B-cell phenotype. Leukemia 17:1589–1595PubMedCrossRef
26.
Zurück zum Zitat Baldus CD, Martus P, Burmeister T, Schwartz S, Gokbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK (2007) Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J Clin Oncol 25:3739–3745. doi:10.1200/JCO.2007.11.5253 PubMedCrossRef Baldus CD, Martus P, Burmeister T, Schwartz S, Gokbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK (2007) Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J Clin Oncol 25:3739–3745. doi:10.​1200/​JCO.​2007.​11.​5253 PubMedCrossRef
27.
Zurück zum Zitat Heuser M, Beutel G, Krauter J, Dohner K, von Neuhoff N, Schlegelberger B, Ganser A (2006) High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 108:3898–3905. doi:10.1182/blood-2006-04-014845 PubMedCrossRef Heuser M, Beutel G, Krauter J, Dohner K, von Neuhoff N, Schlegelberger B, Ganser A (2006) High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 108:3898–3905. doi:10.​1182/​blood-2006-04-014845 PubMedCrossRef
28.
Zurück zum Zitat Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gokbuget N, Hoelzer D, Thiel E, Marschalek R (2009) The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood 113:4011–4015PubMedCrossRef Burmeister T, Meyer C, Schwartz S, Hofmann J, Molkentin M, Kowarz E, Schneider B, Raff T, Reinhardt R, Gokbuget N, Hoelzer D, Thiel E, Marschalek R (2009) The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group. Blood 113:4011–4015PubMedCrossRef
29.
Zurück zum Zitat Burmeister T, Reinhardt R (2008) A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 32:579–585PubMedCrossRef Burmeister T, Reinhardt R (2008) A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 32:579–585PubMedCrossRef
30.
Zurück zum Zitat Langer C, Radmacher MD, Ruppert AS, Whitman SP, Paschka P, Mrozek K, Baldus CD, Vukosavljevic T, Liu CG, Ross ME, Powell BL, de la Chapelle A, Kolitz JE, Larson RA, Marcucci G, Bloomfield CD (2008) High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 111:5371–5379PubMedCrossRef Langer C, Radmacher MD, Ruppert AS, Whitman SP, Paschka P, Mrozek K, Baldus CD, Vukosavljevic T, Liu CG, Ross ME, Powell BL, de la Chapelle A, Kolitz JE, Larson RA, Marcucci G, Bloomfield CD (2008) High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 111:5371–5379PubMedCrossRef
31.
Zurück zum Zitat Marcucci G, Baldus CD, Ruppert AS, Radmacher MD, Mrozek K, Whitman SP, Kolitz JE, Edwards CG, Vardiman JW, Powell BL, Baer MR, Moore JO, Perrotti D, Caligiuri MA, Carroll AJ, Larson RA, de la Chapelle A, Bloomfield CD (2005) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol 23:9234–9242. doi:10.1200/JCO.2005.03.6137 PubMedCrossRef Marcucci G, Baldus CD, Ruppert AS, Radmacher MD, Mrozek K, Whitman SP, Kolitz JE, Edwards CG, Vardiman JW, Powell BL, Baer MR, Moore JO, Perrotti D, Caligiuri MA, Carroll AJ, Larson RA, de la Chapelle A, Bloomfield CD (2005) Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study. J Clin Oncol 23:9234–9242. doi:10.​1200/​JCO.​2005.​03.​6137 PubMedCrossRef
32.
Zurück zum Zitat Baldus CD, Burmeister T, Martus P, Schwartz S, Gokbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK (2006) High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults. J Clin Oncol 24:4714–4720. doi:10.1200/JCO.2006.06.1580 PubMedCrossRef Baldus CD, Burmeister T, Martus P, Schwartz S, Gokbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK (2006) High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults. J Clin Oncol 24:4714–4720. doi:10.​1200/​JCO.​2006.​06.​1580 PubMedCrossRef
33.
34.
Zurück zum Zitat Menssen HD, Renkl HJ, Rodeck U, Maurer J, Notter M, Schwartz S, Reinhardt R, Thiel E (1995) Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia 9:1060–1067PubMed Menssen HD, Renkl HJ, Rodeck U, Maurer J, Notter M, Schwartz S, Reinhardt R, Thiel E (1995) Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia 9:1060–1067PubMed
35.
Zurück zum Zitat Haferlach C, Kern W, Schindela S, Kohlmann A, Alpermann T, Schnittger S, Haferlach T (2011) Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia. Genes Chromosomes Cancer. doi:10.1002/gcc.20950 Haferlach C, Kern W, Schindela S, Kohlmann A, Alpermann T, Schnittger S, Haferlach T (2011) Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia. Genes Chromosomes Cancer. doi:10.​1002/​gcc.​20950
36.
Zurück zum Zitat LeMaistre A, Childs CC, Hirsch-Ginsberg C, Reuben J, Cork A, Trujillo JM, Andersson B, McCredie KB, Freireich E, Stass SA (1988) Heterogeneity in acute undifferentiated leukemia. Hematol Pathol 2:79–90PubMed LeMaistre A, Childs CC, Hirsch-Ginsberg C, Reuben J, Cork A, Trujillo JM, Andersson B, McCredie KB, Freireich E, Stass SA (1988) Heterogeneity in acute undifferentiated leukemia. Hematol Pathol 2:79–90PubMed
37.
Zurück zum Zitat Von LM, Breems D, Van BS, Adriaansen H, Grosveld G (1992) Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer 5:227–234CrossRef Von LM, Breems D, Van BS, Adriaansen H, Grosveld G (1992) Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer 5:227–234CrossRef
39.
Zurück zum Zitat Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, Morilla R, Secker-Walker L, Catovsky D (1996) Cytogenetic findings in acute biphenotypic leukaemia. Leukemia 10:1283–1287PubMed Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, Morilla R, Secker-Walker L, Catovsky D (1996) Cytogenetic findings in acute biphenotypic leukaemia. Leukemia 10:1283–1287PubMed
40.
Zurück zum Zitat Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830PubMedCrossRef Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830PubMedCrossRef
41.
Zurück zum Zitat Burmeister T, Schwartz S, Bartram CR, Gokbuget N, Hoelzer D, Thiel E (2008) Patients' age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 112:918–919. doi:10.1182/blood-2008-04-149286 PubMedCrossRef Burmeister T, Schwartz S, Bartram CR, Gokbuget N, Hoelzer D, Thiel E (2008) Patients' age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 112:918–919. doi:10.​1182/​blood-2008-04-149286 PubMedCrossRef
42.
Zurück zum Zitat Matsumoto Y, Taki T, Fujimoto Y, Taniguchi K, Shimizu D, Shimura K, Uchiyama H, Kuroda J, Nomura K, Inaba T, Shimazaki C, Horiike S, Taniwaki M (2009) Monosomies 7p and 12p and FLT3 internal tandem duplication: possible markers for diagnosis of T/myeloid biphenotypic acute leukemia and its clonal evolution. Int J Hematol 89:352–358. doi:10.1007/s12185-009-0268-7 PubMedCrossRef Matsumoto Y, Taki T, Fujimoto Y, Taniguchi K, Shimizu D, Shimura K, Uchiyama H, Kuroda J, Nomura K, Inaba T, Shimazaki C, Horiike S, Taniwaki M (2009) Monosomies 7p and 12p and FLT3 internal tandem duplication: possible markers for diagnosis of T/myeloid biphenotypic acute leukemia and its clonal evolution. Int J Hematol 89:352–358. doi:10.​1007/​s12185-009-0268-7 PubMedCrossRef
43.
Zurück zum Zitat Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G, Illmer T (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99:4326–4335PubMedCrossRef Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G, Illmer T (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99:4326–4335PubMedCrossRef
44.
Zurück zum Zitat Neumann M, Heesch S, Gokbuget N, Schwartz S, Schlee C, Benlasfer O, Farhadi-Sartangi N, Thibaut J, Burmeister T, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2012) Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations. Blood Cancer J 2:e55PubMedCrossRef Neumann M, Heesch S, Gokbuget N, Schwartz S, Schlee C, Benlasfer O, Farhadi-Sartangi N, Thibaut J, Burmeister T, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2012) Clinical and molecular characterization of early T-cell precursor leukemia: a high-risk subgroup in adult T-ALL with a high frequency of FLT3 mutations. Blood Cancer J 2:e55PubMedCrossRef
45.
Zurück zum Zitat King-Underwood L, Pritchard-Jones K (1998) Wilms' tumor (WT1) gene mutations occur mainly in acute myeloid leukemia and may confer drug resistance. Blood 91:2961–2968PubMed King-Underwood L, Pritchard-Jones K (1998) Wilms' tumor (WT1) gene mutations occur mainly in acute myeloid leukemia and may confer drug resistance. Blood 91:2961–2968PubMed
46.
Zurück zum Zitat Summers K, Stevens J, Kakkas I, Smith M, Smith LL, Macdougall F, Cavenagh J, Bonnet D, Young BD, Lister TA, Fitzgibbon J (2007) Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML. Leukemia 21:550–551. doi:10.1038/sj.leu.2404514 PubMedCrossRef Summers K, Stevens J, Kakkas I, Smith M, Smith LL, Macdougall F, Cavenagh J, Bonnet D, Young BD, Lister TA, Fitzgibbon J (2007) Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML. Leukemia 21:550–551. doi:10.​1038/​sj.​leu.​2404514 PubMedCrossRef
47.
Zurück zum Zitat Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrozek K, Maharry K, Langer C, Baldus CD, Zhao W, Powell BL, Baer MR, Carroll AJ, Caligiuri MA, Kolitz JE, Larson RA, Bloomfield CD (2008) 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 26:4595–4602. doi:10.1200/JCO.2007.15.2058 PubMedCrossRef Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrozek K, Maharry K, Langer C, Baldus CD, Zhao W, Powell BL, Baer MR, Carroll AJ, Caligiuri MA, Kolitz JE, Larson RA, Bloomfield CD (2008) 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 26:4595–4602. doi:10.​1200/​JCO.​2007.​15.​2058 PubMedCrossRef
48.
Zurück zum Zitat Virappane P, Gale R, Hills R, Kakkas I, Summers K, Stevens J, Allen C, Green C, Quentmeier H, Drexler H, Burnett A, Linch D, Bonnet D, Lister TA, Fitzgibbon J (2008) Mutation of the Wilms' tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: the United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 26:5429–5435. doi:10.1200/JCO.2008.16.0333 PubMedCrossRef Virappane P, Gale R, Hills R, Kakkas I, Summers K, Stevens J, Allen C, Green C, Quentmeier H, Drexler H, Burnett A, Linch D, Bonnet D, Lister TA, Fitzgibbon J (2008) Mutation of the Wilms' tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: the United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 26:5429–5435. doi:10.​1200/​JCO.​2008.​16.​0333 PubMedCrossRef
49.
Zurück zum Zitat Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando AA (2009) WT1 mutations in T-ALL. Blood 114:1038–1045. doi:10.1182/blood-2008-12-192039 PubMedCrossRef Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando AA (2009) WT1 mutations in T-ALL. Blood 114:1038–1045. doi:10.​1182/​blood-2008-12-192039 PubMedCrossRef
50.
Zurück zum Zitat Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113:6541–6548. doi:10.1182/blood-2009-02-202598 PubMedCrossRef Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C (2009) A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113:6541–6548. doi:10.​1182/​blood-2009-02-202598 PubMedCrossRef
Metadaten
Titel
Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization
verfasst von
Sandra Heesch
Martin Neumann
Stefan Schwartz
Isabelle Bartram
Cornelia Schlee
Thomas Burmeister
Matthias Hänel
Arnold Ganser
Michael Heuser
Clemens-Martin Wendtner
Wolfgang E. Berdel
Nicola Gökbuget
Dieter Hoelzer
Wolf-Karsten Hofmann
Eckhard Thiel
Claudia D. Baldus
Publikationsdatum
01.06.2013
Verlag
Springer-Verlag
Erschienen in
Annals of Hematology / Ausgabe 6/2013
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-013-1694-4

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