Blood Reviews
Volume 24, Issue 2 , Pages 83-90 , March 2010

Significance of JAK2 and TET2 mutations in myelodysplastic syndromes

References 

  1. Boultwood J, Fidler C, Strickson AJ, et al. Narrowing and genomic annotation of the commonly deleted region of the 5q− syndrome. Blood. 2002;99:4638–4641
  2. Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q− syndrome gene by RNA interference screen. Nature. 2008;451:335–339
  3. Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008;
  4. Jaffe ES, Harris NL, Stein H, Vardiman JW. WHO classification of tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001;
  5. Germing U, Gattermann N, Strupp C, Aivado M, Aul C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res. 2000;24:983–992
  6. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088
  7. Germing U, Strupp C, Knipp S, et al. Chronic myelomonocytic leukemia in the light of the WHO proposals. Haematologica. 2007;92:974–977
  8. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23:7594–7603
  9. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25:3503–3510
  10. Hellstrom-Lindberg E, Malcovati L. Supportive care, growth factors, and new therapies in myelodysplastic syndromes. Blood Rev. 2008;22:75–91
  11. Cazzola M, Invernizzi R, Bergamaschi G, et al. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. 2003;101:1996–2000
  12. Cazzola M, Invernizzi R. Sideroblastic anemias. Clinical hematology. Philadelphia: Mosby Elsevier; 2005;p. 721–32
  13. Camaschella C. Hereditary sideroblastic anemias: pathophysiology, diagnosis, and treatment. Semin Hematol. 2009;46:371–377
  14. Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. Br J Haematol. 2000;108:724–728
  15. Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellstrom-Lindberg E. The WHO classification of MDS does make a difference. Blood. 2004;103:3265–3270
  16. Schmitt-Graeff A, Thiele J, Zuk I, Kvasnicka HM. Essential thrombocythemia with ringed sideroblasts: a heterogeneous spectrum of diseases, but not a distinct entity. Haematologica. 2002;87:392–399
  17. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–951
  18. Guernsey DL, Jiang H, Campagna DR, et al. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet. 2009;41:651–653
  19. Shimada Y, Okuno S, Kawai A, et al. Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia. J Hum Genet. 1998;43:115–122
  20. Pondarre C, Campagna DR, Antiochos B, Sikorski L, Mulhern H, Fleming MD. Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis. Blood. 2007;109:3567–3569
  21. Cavadini P, Biasiotto G, Poli M, et al. RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload. Blood. 2007;109:3552–3559
  22. Boultwood J, Pellagatti A, Nikpour M, et al. The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts. PLoS One. 2008;3:e1970
  23. Steensma DP, Hecksel KA, Porcher JC, Lasho TL. Candidate gene mutation analysis in idiopathic acquired sideroblastic anemia (refractory anemia with ringed sideroblasts). Leuk Res. 2007;31:623–628
  24. Nikpour M, Pellagatti A, Liu A, et al. New insights into the biology of refractory anemia with ring sideroblasts (RARS) and identification of erythroid G-CSF targets by gene expression profiling. Haematologica. 2009;94(Suppl. 2):99
  25. Pellagatti A, Cazzola M, Giagounidis AA, et al. Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype. Blood. 2006;108:337–345
  26. van de Loosdrecht AA, Brada SJ, Blom NR, et al. Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis. Leuk Res. 2001;25:385–393
  27. Shin MG, Kajigaya S, Levin BC, Young NS. Mitochondrial DNA mutations in patients with myelodysplastic syndromes. Blood. 2003;101:3118–3125
  28. Gattermann N, Wulfert M, Junge B, Germing U, Haas R, Hofhaus G. Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome. Blood. 2004;103:1499–1502
  29. Tehranchi R, Fadeel B, Forsblom AM, et al. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood. 2003;101:1080–1086
  30. Claessens YE, Park S, Dubart-Kupperschmitt A, et al. Rescue of early-stage myelodysplastic syndrome-deriving erythroid precursors by the ectopic expression of a dominant-negative form of FADD. Blood. 2005;105:4035–4042
  31. Tehranchi R, Invernizzi R, Grandien A, et al. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood. 2005;106:247–253
  32. Hellstrom-Lindberg E, Schmidt-Mende J, Forsblom AM, Christensson B, Fadeel B, Zhivotovsky B. Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases. Br J Haematol. 2001;112:714–726
  33. Malcovati L, Della Porta MG, Pietra D, et al. Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood. 2009;114:3538–3545
  34. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144–1148
  35. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:e270
  36. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459–468
  37. Szpurka H, Tiu R, Murugesan G, et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood. 2006;108:2173–2181
  38. Boissinot M, Garand R, Hamidou M, Hermouet S. The JAK2–V617F mutation and essential thrombocythemia features in a subset of patients with refractory anemia with ring sideroblasts (RARS). Blood. 2006;108:1781–1782
  39. Ceesay MM, Lea NC, Ingram W, et al. The JAK2 V617F mutation is rare in RARS but common in RARS-T. Leukemia. 2006;20:2060–2061
  40. Ingram W, Lea NC, Cervera J, et al. The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow. Leukemia. 2006;20:1319–1321
  41. Remacha AF, Nomdedeu JF, Puget G, et al. Occurrence of the JAK2 V617F mutation in the WHO provisional entity: myelodysplastic/myeloproliferative disease, unclassifiable-refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica. 2006;91:719–720
  42. Renneville A, Quesnel B, Charpentier A, et al. High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Leukemia. 2006;20:2067–2070
  43. Wang SA, Hasserjian RP, Loew JM, et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features. Leukemia. 2006;20:1641–1644
  44. Gattermann N, Billiet J, Kronenwett R, et al. High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count >600×109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable. Blood. 2007;109:1334–1335
  45. Olsen RJ, Dunphy CH, O’Malley DP, Rice L, Ewton AA, Chang CC. The implication of identifying JAK2 (V617F) in myeloproliferative neoplasms and myelodysplastic syndromes with bone marrow fibrosis. J Hematop. 2008;1:111–117
  46. Raya JM, Arenillas L, Domingo A, et al. Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status. Int J Hematol. 2008;88:387–395
  47. Schmitt-Graeff AH, Teo SS, Olschewski M, et al. JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica. 2008;93:34–40
  48. Schnittger S, Bacher U, Haferlach C, et al. Detection of an MPLW515 mutation in a case with features of both essential thrombocythemia and refractory anemia with ringed sideroblasts and thrombocytosis. Leukemia. 2008;22:453–455
  49. Sokol L, Caceres G, Rocha K, Stockero KJ, Dewald DW, List AF. JAK2(V617F) mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones. Leuk Res 2009 Oct 8 [epub ahead of print].
  50. Buesche G, Teoman H, Wilczak W, et al. Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes. Leukemia. 2008;22:313–322
  51. Hellstrom-Lindberg E, Robert KH, Gahrton G, et al. A predictive model for the clinical response to low dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia. Br J Haematol. 1992;81:503–511
  52. Della Porta MG, Malcovati L, Boveri E, et al. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol. 2009;27:754–762
  53. Gibson SE, Schade AE, Szpurka H, Bak B, Maciejewski JP, Hsi ED. Phospho-STAT5 expression pattern with the MPL W515L mutation is similar to that seen in chronic myeloproliferative disorders with JAK2 V617F. Hum Pathol. 2008;39:1111–1114
  54. Szpurka H, Gondek LP, Mohan SR, Hsi ED, Theil KS, Maciejewski JP. UPD1p indicates the presence of MPL W515L mutation in RARS-T, a mechanism analogous to UPD9p and JAK2 V617F mutation. Leukemia. 2009;23:610–614
  55. Abdel-Wahab O, Mullally A, Hedvat C, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114:144–147
  56. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360:2289–2301
  57. Jankowska AM, Szpurka H, Tiu RV, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113:6403–6410
  58. Kosmider O, Gelsi-Boyer V, Cheok M, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114:3285–3291
  59. Kosmider O, Gelsi-Boyer V, Ciudad M, et al. TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica. 2009;94:1676–1681
  60. Langemeijer SM, Kuiper RP, Berends M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41:838–842
  61. Mohamedali AM, Smith AE, Gaken J, et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol. 2009;27:4002–4006
  62. Tefferi A, Lim KH, Abdel-Wahab O, et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 2009;23:1343–1345
  63. Flach J, Dicker F, Schnittger S, Kohlmann A, Haferlach T, Haferlach C. Mutations of JAK2 and TET2, but not CBL are detectable in a high portion of patients with refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Haematologica 2009 Nov 10 [epub ahead of print].
  64. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–935
  65. Dunbar AJ, Gondek LP, O’Keefe CL, et al. 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res. 2008;68:10349–10357
  66. Makishima H, Cazzolli H, Szpurka H, et al. Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. J Clin Oncol. 2009;27:6109–6116
  67. Reindl C, Quentmeier H, Petropoulos K, et al. CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes. Clin Cancer Res. 2009;15:2238–2247
  68. Gelsi-Boyer V, Trouplin V, Adelaide J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145:788–800
  69. Boultwood J, Perry J, Pellagatti A, Fernandez-Mercado M, Fernandez-Santamaria C, Calasanz MJ, et al. Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia 2010, in press.
  70. Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin+granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120:1037–1046
  71. Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106:803–811
  72. Jadersten M, Malcovati L, Dybedal I, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008;26:3607–3613
  73. Hellstrom-Lindberg E, Cazzola M. The role of JAK2 mutations in RARS and other MDS. Hematology (Am Soc Hematol Educ Program). 2008;52–59

PII: S0268-960X(10)00003-2

doi: 10.1016/j.blre.2010.01.002

Blood Reviews
Volume 24, Issue 2 , Pages 83-90 , March 2010

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