Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The myeloproliferative neoplasms (MPNs) were first recognized by William Dameshek in 1951. The classic MPNs were polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia. They were originally grouped together based on their shared phenotype of myeloproliferation. Since then, important discoveries have been made, identifying a central role of protein tyrosine kinases in the pathogenesis of these disorders. As such, the 2008 WHO diagnostic classification for myeloproliferative neoplasms has incorporated molecular markers with histologic, clinical and laboratory information into the diagnostic algorithms for the MPNs. Important changes include (1) the change of nomenclature of myeloproliferative disorder to myeloproliferative neoplasm emphasizing the clonal nature of these disorders; (2) the classification of mast cell disease as an MPN; (3) the reorganization of the eosinophilic disorders into a molecularly defined category of PDGFRA, PDGFRB and FGFR1-associated myeloid and lymphoid neoplasms with eosinophilia and chronic eosinophilic leukemia, not otherwise specified; and (4) refinement of the diagnostic criteria for PV, ET and PMF incorporating recently described molecular markers, JAK2V617F, JAK2 exon 12 mutations and MPL mutations. This review focuses upon the important changes of the 2008 WHO diagnostic criteria for MPNs.
- Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372–5.
- Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–302. CrossRef
- Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization classification of tumours of hematopoietic and lymphoid tissues. Lyon: IARC Press; 2001.
- Fialkow PJ. Cell lineages in hematopoietic neoplasia studied with glucose-6-phosphate dehydrogenase cell markers. J Cell Physiol Suppl. 1982;1:37–43. CrossRef
- Fialkow PJ, Faguet GB, Jacobson RJ, Vaidya K, Murphy S. Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. Blood. 1981;58:916–9.
- Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L. Polycythemia vera: stem-cell and probable clonal origin of the disease. N Engl J Med. 1976;295:913–6. CrossRef
- Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood. 1978;51:189–94.
- Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007;109:2279–84. CrossRef
- De Keersmaecker K, Cools J. Chronic myeloproliferative disorders: a tyrosine kinase tale. Leukemia. 2006;20:200–5. CrossRef
- Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25:85–109.
- Rowley JD. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243:290–3. CrossRef
- Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994;77:307–16. CrossRef
- Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201–14. CrossRef
- Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, et al. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood. 2004;104:3038–45. CrossRef
- Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, et al. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet. 1998;18:84–7. CrossRef
- Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108:2366–72. CrossRef
- Emanuel PD. Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia. 2008;22:1335–42. CrossRef
- Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–97. CrossRef
- Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054–61.
- Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood. 2005;106:2162–8. CrossRef
- Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–90. CrossRef
- Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, et al. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. 2005;106:3377–9. CrossRef
- James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144–8. CrossRef
- Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459–68. CrossRef
- Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108:3472–6. CrossRef
- Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51. CrossRef
- David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR–ABL-negative chronic myeloproliferative disorders. Blood. 2007;109:61–4. CrossRef
- Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, et al. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood. 2007;109:4635–40. CrossRef
- Orazi A, Germing U. The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia. 2008;22:1308–19. CrossRef
- Atallah E, Nussenzveig R, Yin CC, Bueso-Ramos C, Tam C, Manshouri T, et al. Prognostic interaction between thrombocytosis and JAK2 V617F mutation in the WHO subcategories of myelodysplastic/myeloproliferative disease-unclassifiable and refractory anemia with ringed sideroblasts and marked thrombocytosis. Leukemia. 2008;22:1295–8. CrossRef
- Thiele J, Kvasnicka HM. Hematopathologic findings in chronic idiopathic myelofibrosis. Semin Oncol. 2005;32:380–94. CrossRef
- Thiele J, Kvasnicka HM, Vardiman J. Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl. Best Pract Res Clin Haematol. 2006;19:413–37. CrossRef
- Thiele J, Kvasnicka HM, Zankovich R, Diehl V. The value of bone marrow histology in differentiating between early stage polycythemia vera and secondary (reactive) Polycythemias. Haematologica. 2001;86:368–74.
- Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.
- Wasserman LR. The treatment of polycythemia. A panel discussion. Blood. 1968;32:483–7.
- Murphy S, Iland H, Rosenthal D, Laszlo J. Essential thrombocythemia: an interim report from the Polycythemia Vera Study Group. Semin Hematol. 1986;23:177–82.
- Verstovsek S, Silver RT, Cross NC, Tefferi A. JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less? Leukemia. 2006;20:2067. CrossRef
- Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood. 2005;106:1207–9. CrossRef
- Melzner I, Weniger MA, Menz CK, Moller P. Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia. 2006;20:157–8. CrossRef
- Sulong S, Case M, Minto L, Wilkins B, Hall A, Irving J. The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia. Br J Haematol. 2005;130:964–5. CrossRef
- Tefferi A, Sirhan S, Lasho TL, Schwager SM, Li CY, Dingli D, et al. Concomitant neutrophil JAK2 mutation screening and PRV-1 expression analysis in myeloproliferative disorders and secondary polycythaemia. Br J Haematol. 2005;131:166–71. CrossRef
- McClure RF, Hoyer JD, Mai M. The JAK2 V617F mutation is absent in patients with erythrocytosis due to high oxygen affinity hemoglobin variants. Hemoglobin. 2006;30:487–9. CrossRef
- Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131:208–13. CrossRef
- Tefferi A, Lasho TL, Schwager SM, Steensma DP, Mesa RA, Li CY, et al. The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol. 2005;131:320–8. CrossRef
- 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:e270. CrossRef
- Sidon P, El Housni H, Dessars B, Heimann P. The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors. Leukemia. 2006;20:1622. CrossRef
- Messinezy M, Westwood NB, El-Hemaidi I, Marsden JT, Sherwood RS, Pearson TC. Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia. Br J Haematol. 2002;117:47–53. CrossRef
- Mossuz P, Girodon F, Donnard M, Latger-Cannard V, Dobo I, Boiret N, et al. Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis. Haematologica. 2004;89:1194–8.
- Schnittger S, Bacher U, Haferlach C, Beelen D, Bojko P, Burkle D, et al. Characterization of 35 new cases with four different MPLW515 mutations and essential thrombocytosis or primary myelofibrosis. Haematologica. 2009;94:141–4. CrossRef
- Vannucchi AM, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112:844–7. CrossRef
- Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria
International Journal of Hematology
Volume 91, Issue 2 , pp 174-179
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Myeloproliferative neoplasms
- WHO criteria
- Industry Sectors