Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
International Journal of Hematology
Erschienen in: International Journal of Hematology 6/2018

17.03.2018 | Progress in Hematology

The role of telomere binding molecules for normal and abnormal hematopoiesis

verfasst von: Kentaro Hosokawa, Fumio Arai

Erschienen in: International Journal of Hematology | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.
Literatur
1.
Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C, et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 2007;447:686–90.CrossRefPubMed
2.
Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007;447:725–9.CrossRefPubMed
3.
Sperka T, Wang J, Rudolph KL. DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol. 2012;13:579–90.CrossRefPubMed
4.
Wang J, Sun Q, Morita Y, Jiang H, Groß A, Lechel A, et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell. 2014;158:1444.CrossRefPubMed
5.
Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, et al. Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. 2014;512:198–202.CrossRefPubMedPubMedCentral
6.
Walter D, Lier A, Geiselhart A, Thalheimer FB, Huntscha S, Sobotta MC, et al. Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature. 2015;520:549–52.CrossRefPubMed
7.
Rimmelé P, Liang R, Bigarella CL, Kocabas F, Xie J, Serasinghe MN, et al. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3. EMBO Rep. 2015;16:1164–76.CrossRefPubMedPubMedCentral
8.
Alvarez S, Díaz M, Flach J, Rodriguez-Acebes S, López-Contreras AJ, Martínez D, et al. Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality. Nat Commun. 2015;6:8548.CrossRefPubMedPubMedCentral
9.
Shi W, Vu T, Boucher D, Biernacka A, Nde J, Pandita RK, et al. Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress. Blood. 2017;129:2479–92.CrossRefPubMedPubMedCentral
10.
Szalai VA, Singer MJ, Thorp HH. Site-specific probing of oxidative reactivity and telomerase function using 7,8-dihydro-8-oxoguanine in telomeric DNA. J Am Chem Soc. 2002;124:1625–31.CrossRefPubMed
11.
Gong Y, de Lange T. A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion. Mol Cell. 2010;40:377–87.CrossRefPubMedPubMedCentral
12.
Ray S, Bandaria JN, Qureshi MH, Yildiz A, Balci H. G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding. Proc Natl Acad Sci. 2014;111:2990–5.CrossRefPubMedPubMedCentral
13.
14.
Hosokawa K, MacArthur BD, Ikushima YM, Toyama H, Masuhiro Y, Hanazawa S, et al. The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Nat Commun. 2017;8:804.CrossRefPubMedPubMedCentral
15.
Wang J, Lu X, Sakk V, Klein CA, Rudolph KL. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood. 2014;124:3237–40.CrossRefPubMedPubMedCentral
16.
Jones M, Osawa G, Regal JA, Weinberg DN, Taggart J, Kocak H, et al. Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation. J Clin Investig. 2014;124:353–66.CrossRefPubMed
17.
Wang Y, Sharpless N, Chang S. p16INK4a protects against dysfunctional telomere-induced ATR-dependent DNA damage responses. J Clin Investig. 2013;123:4489–501.CrossRefPubMedPubMedCentral
18.
Beier F, Foronda M, Martinez P, Blasco MA. Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita. Blood. 2012;120:2990–3000.CrossRefPubMedPubMedCentral
19.
Ju Z, Zhang J, Gao Y, Cheng T. Telomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging. Int J Hematol. 2011;94:33–43.CrossRefPubMed
20.
Wang RC, Smogorzewska A, de Lange T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell. 2004;119:355–68.CrossRefPubMed
21.
Doksani Y, Wu JY, De Lange T, Zhuang X. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell. 2013;155:345–56.CrossRefPubMedPubMedCentral
22.
23.
24.
Frescas D, de Lange T. Binding of TPP1 protein to TIN2 protein is required for POT1a, b protein-mediated telomere protection. J Biol Chem. 2014;289:24180–7.CrossRefPubMedPubMedCentral
25.
Frescas D, de Lange T. A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice. Genes Dev. 2014;28:153–66.CrossRefPubMedPubMedCentral
26.
Erdel F, Kratz K, Willcox S, Griffith JD, Greene EC, de Lange T. Telomere recognition and assembly mechanism of mammalian shelterin. Cell Rep. 2017;18:41–53.CrossRefPubMedPubMedCentral
27.
Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, et al. The POT1–TPP1 telomere complex is a telomerase processivity factor. Nature. 2007;445:506–10.CrossRefPubMed
28.
Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, et al. TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase. Nature. 2007;445:559–62.CrossRefPubMed
29.
Court R, Chapman L, Fairall L, Rhodes D. How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: a view from high-resolution crystal structures. EMBO Rep. 2005;6:39–45.CrossRefPubMed
30.
Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, et al. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell. 2009;138:90–103.CrossRefPubMedPubMedCentral
31.
van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997;385:740–3.CrossRefPubMed
32.
Wu Y, Xiao S, Zhu X-D. MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control. Nat Struct Mol Biol. 2007;14:832–40.CrossRefPubMed
33.
34.
Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448:1068–71.CrossRefPubMed
35.
Celli GB, Denchi EL, de Lange T. Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol. 2006;8:885–90.CrossRefPubMed
36.
Bae NS, Baumann P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell. 2007;26:323–34.CrossRefPubMed
37.
Sfeir A, Kabir S, van Overbeek M, Celli GB, de Lange T. Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science. 2010;327:1657–61.CrossRefPubMedPubMedCentral
38.
Rai R, Chen Y, Lei M, Chang S. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nat Commun. 2016;7:10881.CrossRefPubMedPubMedCentral
39.
Martinez P, Thanasoula M, Carlos AR, Gómez-López G, Tejera AM, Schoeftner S, et al. Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol. 2010;12:768–80.CrossRefPubMedPubMedCentral
40.
41.
Abreu E, Aritonovska E, Reichenbach P, Cristofari G, Culp B, Terns RM, et al. TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. Mol Cell Biol. 2010;30:2971–82.CrossRefPubMedPubMedCentral
42.
Zhong FL, Batista LFZ, Freund A, Pech MF, Venteicher AS, Artandi SE. TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell. 2012;150:481–94.CrossRefPubMedPubMedCentral
43.
Dalby AB, Hofr C, Cech TR. Contributions of the TEL-patch amino acid cluster on TPP1 to telomeric DNA synthesis by human telomerase. J Mol Biol. 2015;427:1291–303.CrossRefPubMedPubMedCentral
44.
Nandakumar J, Bell CF, Weidenfeld I, Zaug AJ, Leinwand LA, Cech TR. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature. 2012;492:285–9.CrossRefPubMedPubMedCentral
45.
Schmidt JC, Zaug AJ, Cech TR. Live cell imaging reveals the dynamics of telomerase recruitment to telomeres. Cell. 2016;166(1188–1197):e9.
46.
Lei M, Podell ER, Baumann P, Cech TR. DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA. Nature. 2003;426:198–203.CrossRefPubMed
47.
Lei M, Podell ER, Cech TR. Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol. 2004;11:1223–9.CrossRefPubMed
48.
Flynn RL, Centore RC, O’Sullivan RJ, Rai R, Tse A, Songyang Z, et al. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature. 2011;471:532–6.CrossRefPubMedPubMedCentral
49.
Hockemeyer D, Daniels J-P, Takai H, de Lange T. Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell. 2006;126:63–77.CrossRefPubMed
50.
Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, et al. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell. 2006;126:49–62.CrossRefPubMed
51.
He H, Multani AS, Cosme-Blanco W, Tahara H, Ma J, Pathak S, et al. POT1b protects telomeres from end-to-end chromosomal fusions and aberrant homologous recombination. EMBO J. 2006;25:5180–90.CrossRefPubMedPubMedCentral
52.
Wu P, Takai H, de Lange T. Telomeric 3′ overhangs derive from resection by Exo1 and apollo and fill-in by POT1b-associated CST. Cell. 2012;150:39–52.CrossRefPubMedPubMedCentral
53.
Guo X, Deng Y, Lin Y, Cosme-Blanco W, Chan S, He H, et al. Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. EMBO J. 2007;26:4709–19.CrossRefPubMedPubMedCentral
54.
He H, Wang Y, Guo X, Ramchandani S, Ma J, Shen M-F, et al. Pot1b deletion and telomerase haploinsufficiency in mice initiate an ATR-dependent DNA damage response and elicit phenotypes resembling dyskeratosis congenita. Mol Cell Biol. 2009;29:229–40.CrossRefPubMed
55.
El Maï M, Wagner K-D, Michiels J-F, Ambrosetti D, Borderie A, Destree S, et al. The telomeric protein TRF2 regulates angiogenesis by binding and activating the PDGFRβ promoter. Cell Rep. 2014;9:1047–60.CrossRefPubMed
56.
Diala I, Wagner N, Magdinier F, Shkreli M, Sirakov M, Bauwens S, et al. Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Rep. 2013;14:356–63.CrossRefPubMedPubMedCentral
57.
Martínez P, Gómez-López G, García F, Mercken E, Mitchell S, Flores JM, et al. RAP1 protects from obesity through its extratelomeric role regulating gene expression. Cell Rep. 2013;3:2059–74.CrossRefPubMedPubMedCentral
58.
Teo H, Ghosh S, Luesch H, Ghosh A, Wong ET, Malik N, et al. Telomere-independent Rap1 is an IKK adaptor and regulates NF-κB-dependent gene expression. Nat Cell Biol. 2010;12:758–67.CrossRefPubMed
59.
Chen L-Y, Zhang Y, Zhang Q, Li H, Luo Z, Fang H, et al. Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol Cell. 2012;47:839–50.CrossRefPubMedPubMedCentral
60.
Martinez P, Thanasoula M, Munoz P, Liao C, Tejera A, McNees C, et al. Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev. 2009;23:2060–75.CrossRefPubMedPubMedCentral
61.
Bär C, Povedano JM, Serrano R, Benitez-Buelga C, Popkes M, Formentini I, et al. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. Blood. 2016;127:1770–9.CrossRefPubMed
62.
Kibe T, Osawa GA, Keegan CE, de Lange T. Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol. 2010;30:1059–66.CrossRefPubMed
63.
Keegan CE, Hutz JE, Else T, Adamska M, Shah SP, Kent AE, et al. Urogenital and caudal dysgenesis in adrenocortical dysplasia (Acd) mice is caused by a splicing mutation in a novel telomeric regulator. Hum Mol Genet. 2005;14:113–23.CrossRefPubMed
64.
Hockemeyer D, Palm W, Wang RC, Couto SS, de Lange T. Engineered telomere degradation models dyskeratosis congenita. Genes Dev. 2008;22:1773–85.CrossRefPubMedPubMedCentral
65.
66.
Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature. 2006;443:421–6.CrossRefPubMed
67.
Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, et al. Increasing p16 INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature. 2006;443:448–52.CrossRefPubMedPubMedCentral
68.
Wang Y, Wang X, Flores ER, Yu J, Chang S. Dysfunctional telomeres induce p53-dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation. Aging Cell. 2016;15:646–60.CrossRefPubMedPubMedCentral
69.
Choi KH, Lakamp-Hawley AS, Kolar C, Yan Y, Borgstahl GEO, Ouellette MM. The OB-fold domain 1 of human POT1 recognizes both telomeric and non-telomeric DNA motifs. Biochimie. 2015;115:17–27.CrossRefPubMedPubMedCentral
70.
Cesare AJ, Hayashi MT, Crabbe L, Karlseder J. The telomere deprotection response is functionally distinct from the genomic DNA damage response. Mol Cell. 2013;51:141–55.CrossRefPubMedPubMedCentral
71.
Campbell LJ, Fidler C, Eagleton H, Peniket A, Kusec R, Gal S, et al. hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia. Leukemia. 2006;20:671–9.CrossRefPubMed
72.
Poncet D, Belleville A, de t’Kint Roodenbeke CTK, de Climens AR, Ben Simon E, Merle-Beral H, et al. Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia. Blood. 2008;111:2388–91.CrossRefPubMed
73.
Ohyashiki JH, Hayashi S, Yahata N, Iwama H, Ando K, Tauchi T, et al. Impaired telomere regulation mechanism by TRF1 (telomere-binding protein), but not TRF2 expression, in acute leukemia cells. Int J Oncol. 2001;18:593–8.PubMed
74.
Yamada K, Yagihashi A, Yamada M, Asanuma K, Moriai R, Kobayashi D, et al. Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells. Anticancer Res. 2002;22:1315–20.PubMed
75.
Capraro V, Zane L, Poncet D, Perol D, Galia P, Preudhomme C, et al. Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemias. Exp Hematol. 2011;39(195–202):e2.
76.
Begemann S, Galimi F, Karlseder J. Moderate expression of TRF2 in the hematopoietic system increases development of large cell blastic T-cell lymphomas. Aging (Albany NY). 2009;1:122–30.CrossRef
77.
Augereau A, de t’Kint Roodenbeke C, Simonet T, Bauwens S, Horard B, Callanan M, et al. Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation. Blood. 2011;118:1316–22.CrossRefPubMed
78.
Guo Y, Kartawinata M, Li J, Pickett HA, Teo J, Kilo T, et al. Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1. Blood. 2014;124:2767–74.CrossRefPubMedPubMedCentral
79.
Wang T, Mei SC, Fu R, Wang HQ, Shao ZH. Expression of Shelterin component POT1 is associated with decreased telomere length and immunity condition in humans with severe aplastic anemia. J Immunol Res. 2014;2014:439530.PubMedPubMedCentral
80.
Panero J, Stanganelli C, Arbelbide J, Fantl DB, Kohan D, Rivello HG, et al. Expression profile of shelterin components in plasma cell disorders. Clinical significance of POT1 overexpression. Blood Cells Mol Dis. 2014;52:134–9.CrossRefPubMed
81.
82.
Glousker G, Touzot F, Revy P, Tzfati Y, Savage SA. Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder. Br J Haematol. 2015;170:457–71.CrossRefPubMedPubMedCentral
83.
Savage SA, Bertuch AA. The genetics and clinical manifestations of telomere biology disorders. Genet Med. 2010;12:753–64.CrossRefPubMed
84.
Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet. 2008;82:501–9.CrossRefPubMedPubMedCentral
85.
Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112:3594–600.CrossRefPubMedPubMedCentral
86.
Canudas S, Houghtaling BR, Bhanot M, Sasa G, Savage SA, Bertuch AA, et al. A role for heterochromatin protein 1γ at human telomeres. Genes Dev. 2011;25:1807–19.CrossRefPubMedPubMedCentral
87.
Frank AK, Tran DC, Qu RW, Stohr BA, Segal DJ, Xu L. The shelterin TIN2 subunit mediates recruitment of telomerase to telomeres. PLoS Genet. 2015;11:e1005410.CrossRefPubMedPubMedCentral
88.
Canudas S, Smith S. Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells. J Cell Biol. 2009;187:165–73.CrossRefPubMedPubMedCentral
89.
90.
Kocak H, Ballew BJ, Bisht K, Eggebeen R, Hicks BD, Suman S, et al. Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1. Genes Dev. 2014;28:2090–102.CrossRefPubMedPubMedCentral
91.
Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 2012;44:47–52.CrossRef
92.
Ramsay AJ, Quesada V, Foronda M, Conde L, Martínez-Trillos A, Villamor N, et al. POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia. Nat Genet. 2013;45:526–30.CrossRefPubMed
93.
Gu P, Wang Y, Bisht KK, Wu L, Kukova L, Smith EM, et al. Pot1 OB-fold mutations unleash telomere instability to initiate tumorigenesis. Oncogene. 2017;36:1939–51.CrossRefPubMed
94.
Tumorigenesis IA, Pinzaru AM, Hom RA, Beal A, Wuttke DS, Pinzaru AM, et al. Telomere replication stress induced by POT1 article telomere replication stress induced by POT1 inactivation accelerates tumorigenesis. Cell Rep. 2016;15:2170–84.CrossRef
Metadaten
Titel
The role of telomere binding molecules for normal and abnormal hematopoiesis
verfasst von
Kentaro Hosokawa
Fumio Arai
Publikationsdatum
17.03.2018
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 6/2018
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-018-2432-4

Weitere Artikel der Ausgabe 6/2018

International Journal of Hematology 6/2018 Zur Ausgabe

Case Report

Three coexisting lymphomas in a single patient: composite lymphoma derived from a common germinal center B-cell precursor and unrelated discordant lymphoma

Progress in Hematology

Regulation of unfolded protein response in hematopoietic stem cells

Case Report

Successful treatment of follicular lymphoma with second-generation tyrosine kinase inhibitors administered for coexisting chronic myeloid leukemia

Progress in Hematology

The hematopoietic stem cell diet

Letter to the Editor

Severe graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with residual mogamulizumab concentration

Original Article

Characteristics and outcome of chronic myeloid leukemia patients with E255K/V BCR–ABL kinase domain mutations

Neu im Fachgebiet Onkologie

17.04.2024 | Mammakarzinom | Nachrichten

Adjuvante Brustkrebstherapie: Doppelt hält besser

16.04.2024 | Maligne primäre ZNS-Tumoren | Nachrichten

Manche Gestagene können das Risiko für Meningeome erhöhen

10.04.2024 | PSA-Screening | Nachrichten

Einladung zum PSA-Screening senkt die Krebssterblichkeit

09.04.2024 | DGP 2024 | Kongressbericht | Nachrichten

Chemotherapie mit Hindernissen
weitere anzeigen

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen