myeloproliferative disorders

Summary

Summary: Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.

Top Publications

  1. Bochtler T, Kirsch M, Maier B, Bachmann J, Klingmuller U, Anderhub S, et al. Centrosomal targeting of tyrosine kinase activity does not enhance oncogenicity in chronic myeloproliferative disorders. Leukemia. 2012;26:728-35 pubmed publisher
    ..kinase activation by reciprocal chromosomal translocation is a common pathogenetic mechanism in chronic myeloproliferative disorders. Since centrosomal proteins have been recurrently identified as translocation partners of tyrosine ..
  2. Vannucchi A, Pieri L, Susini M, Guglielmelli P. BCR-ABL1-negative chronic myeloid neoplasms: an update on management techniques. Future Oncol. 2012;8:575-93 pubmed publisher
    ..This review discusses how to manage, according to current clinical practice, the steps of diagnosis, prognostication and therapeutic choices in myeloproliferative neoplasm patients...
  3. Bogani C, Bartalucci N, Martinelli S, Tozzi L, Guglielmelli P, Bosi A, et al. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms. PLoS ONE. 2013;8:e54826 pubmed publisher
    ..The aim of the study was to characterize the effects in vitro of mTOR inhibitors, used alone and in combination with JAK2 inhibitors, against MPN cells...
  4. Passamonti F, Maffioli M, Caramazza D. New generation small-molecule inhibitors in myeloproliferative neoplasms. Curr Opin Hematol. 2012;19:117-23 pubmed publisher
    ..Myeloproliferative neoplasms (MPNs) are diseases that carry the JAK2 (V617F) mutation in about 70% of the patients. The purpose of this review is to describe the recent advances in the therapy of MPNs with JAK2 inhibitors...
  5. Shih A, Abdel Wahab O, Patel J, Levine R. The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer. 2012;12:599-612 pubmed publisher
  6. Reddy M, Deshpande A, Sattler M. Targeting JAK2 in the therapy of myeloproliferative neoplasms. Expert Opin Ther Targets. 2012;16:313-24 pubmed publisher
    ..MPNs are frequently associated with activating mutations in JAK2; small-molecule drugs targeting this molecule have entered clinical trials...
  7. Lange T, Edelmann A, Siebolts U, Krahl R, Nehring C, Jäkel N, et al. JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogeneic stem cell transplantation significantly predicts outcome and risk of relapse. Haematologica. 2013;98:722-8 pubmed publisher
    ..As this might provide an important tool in early management of imminent early relapse it will be important to define consensus guidelines for optimal monitoring...
  8. Puda A, Milosevic J, Berg T, Klampfl T, Harutyunyan A, Gisslinger B, et al. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. Am J Hematol. 2012;87:245-50 pubmed publisher
    ..Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders...
  9. Jovanovic J, Ivey A, Vannucchi A, Lippert E, Oppliger Leibundgut E, Cassinat B, et al. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM. Leukemia. 2013;27:2032-9 pubmed publisher
    ..This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant...

More Information

Publications81

  1. Chim C, Wan T, Wong K, Fung T, Drexler H, Wong K. Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms. J Transl Med. 2011;9:197 pubmed publisher
    ..MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis...
  2. Score J, Hidalgo Curtis C, Jones A, Winkelmann N, Skinner A, Ward D, et al. Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms. Blood. 2012;119:1208-13 pubmed publisher
    ..All 3 SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes...
  3. Haferlach C, Bacher U, Schnittger S, Alpermann T, Zenger M, Kern W, et al. ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events. Genes Chromosomes Cancer. 2012;51:328-37 pubmed publisher
    ..Our study confirms the variety of ETV6 rearrangements in AML, MDS, and MPNs often in association with other genetic events. Prognosis of ETV6 rearranged de novo AML seems to be intermediate, which should be independently confirmed...
  4. Fiskus W, Verstovsek S, Manshouri T, Smith J, Peth K, Abhyankar S, et al. Dual PI3K/AKT/mTOR inhibitor BEZ235 synergistically enhances the activity of JAK2 inhibitor against cultured and primary human myeloproliferative neoplasm cells. Mol Cancer Ther. 2013;12:577-88 pubmed publisher
    ..These findings create a compelling rationale to determine the in vivo activity of dual PI3K/mTOR inhibitors in combination with JAK inhibitors against myelofibrosis HPCs...
  5. Hasan S, Lacout C, Marty C, Cuingnet M, Solary E, Vainchenker W, et al. JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFN?. Blood. 2013;122:1464-77 pubmed publisher
  6. Bench A, White H, Foroni L, Godfrey A, Gerrard G, Akiki S, et al. Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations. Br J Haematol. 2013;160:25-34 pubmed publisher
    ..Molecular results should be considered in the context of clinical findings and other haematological or laboratory results. ..
  7. Lafave L, Levine R. JAK2 the future: therapeutic strategies for JAK-dependent malignancies. Trends Pharmacol Sci. 2012;33:574-82 pubmed publisher
    ..These innovative therapies may translate to treatment of other diseases that are dependent on JAK signaling, including B-precursor acute lymphoblastic leukemia (B-ALL)...
  8. Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, et al. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature. 2012;489:155-9 pubmed publisher
    ..Consequently, therapies that result in JAK2 degradation retain efficacy in persistent cells and may provide additional benefit to patients with JAK2-dependent malignancies treated with JAK2 inhibitors...
  9. Cross N. Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2011;2011:208-14 pubmed publisher
    ..This review summarizes the established facts relating to the genetics of MPNs, but highlights recent findings and areas of controversy...
  10. Lundberg P, Karow A, Nienhold R, Looser R, Hao Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123:2220-8 pubmed publisher
    ..Our data show that comprehensive mutational screening at diagnosis and during follow-up has considerable potential to identify patients at high risk of disease progression. ..
  11. Weigert O, Lane A, Bird L, Kopp N, Chapuy B, Van Bodegom D, et al. Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. J Exp Med. 2012;209:259-73 pubmed publisher
    ..Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors...
  12. Schnittger S, Bacher U, Alpermann T, Reiter A, Ulke M, Dicker F, et al. Use of CBL exon 8 and 9 mutations in diagnosis of myeloproliferative neoplasms and myelodysplastic/myeloproliferative disorders: an analysis of 636 cases. Haematologica. 2012;97:1890-4 pubmed publisher
    ..Therefore, CBL(mut) are frequent in chronic myelomonocytic leukemia, absent in classical myeloproliferative neoplasms, and are only exceptionally found in coincidence with JAK-STAT pathway activating mutations...
  13. Hultcrantz M, Kristinsson S, Andersson T, Landgren O, Eloranta S, Derolf A, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol. 2012;30:2995-3001 pubmed publisher
    ..We conducted a large population-based study to establish patterns of survival in more than 9,000 patients with MPNs...
  14. Barbui T, Finazzi G, Falanga A. Myeloproliferative neoplasms and thrombosis. Blood. 2013;122:2176-84 pubmed publisher
    ..Whether novel drugs targeting the constitutively active JAK2/STAT pathway will improve the management of thrombosis is a challenge for future studies. ..
  15. Khan I, Huang Z, Wen Q, Stankiewicz M, Gilles L, Goldenson B, et al. AKT is a therapeutic target in myeloproliferative neoplasms. Leukemia. 2013;27:1882-90 pubmed publisher
    ..Together, these findings establish AKT as a rational therapeutic target in the MPNs. ..
  16. Milosevic J, Kralovics R. Genetic and epigenetic alterations of myeloproliferative disorders. Int J Hematol. 2013;97:183-97 pubmed publisher
    ..This review provides an overview of point mutations and cytogenetic lesions associated with MPN and addresses the role of these somatic lesions in MPN disease progression...
  17. Westerterp M, Gourion Arsiquaud S, Murphy A, Shih A, Cremers S, Levine R, et al. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell. 2012;11:195-206 pubmed publisher
    ..Our data identify a role of cholesterol efflux pathways in the control of HSPC mobilization. This may translate into therapeutic strategies for atherosclerosis and hematologic malignancies...
  18. Nielsen C, Birgens H, Nordestgaard B, Bojesen S. Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population. Br J Haematol. 2013;160:70-9 pubmed publisher
    ..In conclusion, in the general population the JAK2 V617F somatic mutation has a high diagnostic value for myeloproliferative cancer when combined with conventional haematological parameters...
  19. Schnittger S, Bacher U, Eder C, Dicker F, Alpermann T, Grossmann V, et al. Molecular analyses of 15,542 patients with suspected BCR-ABL1-negative myeloproliferative disorders allow to develop a stepwise diagnostic workflow. Haematologica. 2012;97:1582-5 pubmed publisher
    ..In cases in which a myeloproliferative neoplasm cannot be established, analysis for TET2, CBL and EZH2 mutations may be indicated...
  20. Brecqueville M, Rey J, Bertucci F, Coppin E, Finetti P, Carbuccia N, et al. Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes Chromosomes Cancer. 2012;51:743-55 pubmed publisher
    ..We found a high incidence of ASXL1 mutation in MF patients (20%) and a low incidence in PV (7%) and ET (4%) patients. Mutations in the other genes were rare (CBL, DNMT3A, IDH2, MPL, SF3B1, SUZ12, NF1) or absent (IDH1)...
  21. Gelsi Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci M, Birnbaum D. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol. 2012;5:12 pubmed publisher
    ..They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment...
  22. Kaufmann K, Gründer A, Hadlich T, Wehrle J, Gothwal M, Bogeska R, et al. A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. J Exp Med. 2012;209:35-50 pubmed publisher
    ..These data establish a role for NF-E2 in the pathophysiology of MPNs and provide a molecular rationale for investigating epigenetic alterations as novel targets for rationally designed MPN therapies...
  23. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan A, Milosevic J, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123:1544-51 pubmed publisher
  24. Tian Z, Zhu P, Liu H, Chen Y, Wang F, Zhang Y, et al. [Relationship between V617F mutation and 46/1 haplotype in JAK2 gene in patients with chronic myeloproliferative diseases and frequencies of 46/1 haplotype in different Chinese nationalities]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20:362-7 pubmed
    ..In more than half of Chinese V617F-positive MPD patients, the V617F mutation locates in 46/1 haplotype in JAK2. The frequencies of 46/1 haplotype are statistically insignificant among Han, Tibetan and Yugu nationality populations...
  25. Chen E, Beer P, Godfrey A, Ortmann C, Li J, Costa Pereira A, et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell. 2010;18:524-35 pubmed publisher
    ..Our results illustrate the power of clonal analysis, indicate that the consequences of JAK2V617F reflect a balance between STAT5 and STAT1 activation and are relevant for other neoplasms associated with signaling pathway mutations. ..
  26. Gery S, Cao Q, Gueller S, Xing H, Tefferi A, Koeffler H. Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F. J Leukoc Biol. 2009;85:957-65 pubmed publisher
    The JAK2 mutation JAK2V617F is found frequently in patients with myeloproliferative disorders (MPD) and transforms hematopoietic cells to cytokine-independent proliferation when expressed with specific cytokine receptors...
  27. Vannucchi A, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia. 2008;22:1299-307 pubmed publisher
  28. da Costa Reis Monte Mór B, Plo I, da Cunha A, Costa G, de Albuquerque D, Jedidi A, et al. Constitutive JunB expression, associated with the JAK2 V617F mutation, stimulates proliferation of the erythroid lineage. Leukemia. 2009;23:144-52 pubmed publisher
    ..These results establish a role for JunB in normal erythropoiesis and indicate that JunB may play a major role in the development of JAK2 V617F myeloproliferative disorders.
  29. Pardanani A, Fridley B, Lasho T, Gilliland D, Tefferi A. Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood. 2008;111:2785-9 pubmed
    ..Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele.
  30. Moliterno A, Williams D, Rogers O, Isaacs M, Spivak J. Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens. Exp Hematol. 2008;36:1480-6 pubmed publisher
    The myeloproliferative disorders (MPD), polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), differ phenotypically, but share the same JAK2(V617F) mutation...
  31. Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia. 2008;22:905-14 pubmed publisher
    Among the 'classic' BCR/ABL-negative chronic myeloproliferative disorders, primary myelofibrosis (PMF) is associated with a substantial life-expectancy reduction...
  32. Makishima H, Cazzolli H, Szpurka H, Dunbar A, Tiu R, Huh J, et al. Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. J Clin Oncol. 2009;27:6109-16 pubmed publisher
  33. Vannucchi A, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-91 pubmed publisher
    ..In the current article, the authors provide a clinically oriented overview of MPNs in terms of their molecular pathogenesis, classification, diagnosis, and management. ..
  34. Chim C, Wan T, Fung T, Wong K. Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms. J Clin Pathol. 2010;63:942-6 pubmed publisher
    ..In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at diagnosis. The role of methylation of these genes at the time of leukaemic transformation warrants further study. ..
  35. Najfeld V, Cozza A, Berkofsy Fessler W, Prchal J, Scalise A. Numerical gain and structural rearrangements of JAK2, identified by FISH, characterize both JAK2617V>F-positive and -negative patients with Ph-negative MPD, myelodysplasia, and B-lymphoid neoplasms. Exp Hematol. 2007;35:1668-76 pubmed
    ..patients with 9p24 chromosomal rearrangements or patients with Philadelphia chromosome (Ph)-negative myeloproliferative disorders (MPDs), with or without +9/+9p chromosomal abnormalities, might demonstrate additional and/or cryptic ..
  36. Tefferi A. Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1. J Cell Mol Med. 2009;13:215-37 pubmed publisher
    ..The current review discusses the above listed mutant molecules in the context of their value as drug targets. ..
  37. Pardanani A, Vannucchi A, Passamonti F, Cervantes F, Barbui T, Tefferi A. JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia. 2011;25:218-25 pubmed publisher
  38. Stegelmann F, Bullinger L, Griesshammer M, Holzmann K, Habdank M, Kuhn S, et al. High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations. Haematologica. 2010;95:666-9 pubmed publisher
    ..Further analyses on single-gene level are necessary to uncover the mechanisms that are involved in the pathogenesis of myeloproliferative neoplasms. ..
  39. Saint Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, et al. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009;114:1628-32 pubmed publisher
    ..TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia. ..
  40. Richebourg S, Theisen O, Plantier I, Parry A, Soenen Cornu V, Lepelley P, et al. Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal cytogenetic evolution of authentic chronic myelogeneous leukemia. Genes Chromosomes Cancer. 2008;47:915-8 pubmed publisher
  41. Lippert E, Girodon F, Hammond E, Jelinek J, Reading N, Fehse B, et al. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica. 2009;94:38-45 pubmed publisher
    ..Techniques expressing the allelic burden as JAK2V617F/total JAK2 and using a common set of standards produced similar quantification results but with variable sensitivity. Calibration to a reference standard improved reproducibility. ..
  42. Ghoreschi K, Laurence A, O Shea J. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273-87 pubmed publisher
    ..transformation, the most common being gain-of-function mutations of Jak2 in polycythemia vera and other myeloproliferative disorders. Our existing knowledge on Jak signaling pathways and fundamental work on their biochemical structure ..
  43. Jackson C, Medeiros L, Miranda R. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010;41:461-76 pubmed publisher
    ..The most common partner is ZNF198 on chromosome 13q12. In the current World Health Organization classification, the 8p11 myeloproliferative syndrome is designated as "myeloid and lymphoid neoplasms with FGFR1 abnormalities." ..
  44. Morgan K, Gilliland D. A role for JAK2 mutations in myeloproliferative diseases. Annu Rev Med. 2008;59:213-22 pubmed
    b>Myeloproliferative disorders (MPDs) are characterized by a clonal expansion of myeloid cells...
  45. Ricci C, Fermo E, Corti S, Molteni M, Faricciotti A, Cortelezzi A, et al. RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant. Clin Cancer Res. 2010;16:2246-56 pubmed publisher
  46. Quintas Cardama A, Kantarjian H, Cortes J, Verstovsek S. Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov. 2011;10:127-40 pubmed publisher
    ..Preliminary results indicate that these agents hold great promise for the treatment of JAK-driven disorders...
  47. Tefferi A. Essential thrombocythemia, polycythemia vera, and myelofibrosis: current management and the prospect of targeted therapy. Am J Hematol. 2008;83:491-7 pubmed publisher
    ..Herein, I will first outline my views regarding current management in ET, PV, and PMF and then discuss emerging data on preclinical and clinical activity of anti-JAK2 small molecule drugs. Am. J. Hematol., 2008. (c) 2008 Wiley-Liss, Inc...
  48. Ren M, Cowell J. Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease. Blood. 2011;117:6837-47 pubmed publisher
    ..These data demonstrate the importance of Notch signaling in the etiology of SCLL, and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients...
  49. Ma W, Kantarjian H, Zhang X, Yeh C, Zhang Z, Verstovsek S, et al. Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias. J Mol Diagn. 2009;11:49-53 pubmed publisher
    ..Furthermore, mutation screening using RNA is highly sensitive and could replace DNA-based testing because of the relative abundance of target transcripts and the ease in detecting deletion of the entire exon. ..
  50. Naramura M, Nandwani N, Gu H, Band V, Band H. Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells. Proc Natl Acad Sci U S A. 2010;107:16274-9 pubmed publisher
    ..Thus, Cbl and Cbl-b play redundant but essential roles in HSC regulation, whose breakdown leads to hematological abnormalities that phenocopy crucial aspects of mutant Cbl-driven human myeloid malignancies...
  51. Jankowska A, Szpurka H, Tiu R, Makishima H, Afable M, Huh J, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113:6403-10 pubmed publisher
    ..The frequency of mutations in this candidate myeloid regulatory gene suggests an important role in the pathogenesis of poor prognosis MDS/MPN and sAML and may act as a disease gene marker for these often cytogenetically normal disorders...
  52. Xiao W, Hong H, Kawakami Y, Kato Y, Wu D, Yasudo H, et al. Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell. 2009;16:161-71 pubmed publisher
    ..The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-beta3 is likely a tumor suppressor...
  53. Couronné L, Lippert E, Andrieux J, Kosmider O, Radford Weiss I, Penther D, et al. Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia. 2010;24:201-3 pubmed publisher
  54. Tefferi A, Skoda R, Vardiman J. Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. Nat Rev Clin Oncol. 2009;6:627-37 pubmed publisher
    ..We discuss histologic, cytogenetic and molecular changes in MPN and illustrate their integration into practical diagnostic algorithms...
  55. Chan G, Kalaitzidis D, Usenko T, Kutok J, Yang W, Mohi M, et al. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Blood. 2009;113:4414-24 pubmed publisher
    ..Our studies provide a mouse model for Ptpn11-evoked MPD and show that this disease results from cell-autonomous and distinct lineage-specific effects of mutant Ptpn11 on multiple stages of hematopoiesis...
  56. Vainchenker W, Delhommeau F, Constantinescu S, Bernard O. New mutations and pathogenesis of myeloproliferative neoplasms. Blood. 2011;118:1723-35 pubmed publisher
    ..Their precise roles in hematopoiesis and in the pathogenesis of MPN, as well as their prognostic impact and potential as a therapeutic target, are currently under investigation...
  57. Atallah E, Nussenzveig R, Yin C, 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 pubmed
  58. Scherber R, Dueck A, Johansson P, Barbui T, Barosi G, Vannucchi A, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011;118:401-8 pubmed publisher
    ..7). The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally...
  59. Wang W, Schwemmers S, Hexner E, Pahl H. AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2. Blood. 2010;116:254-66 pubmed publisher
    ..Our data identify NF-E2 as a novel AML1 target gene and delineate a role for aberrant AML1 expression in mediating elevated NF-E2 expression in MPN patients...
  60. Beer P, Campbell P, Scott L, Bench A, Erber W, Bareford D, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood. 2008;112:141-9 pubmed publisher
    ..MPL mutations lacked prognostic significance with respect to thrombosis, major hemorrhage, myelofibrotic transformation or survival...
  61. Grimwade L, Happerfield L, Tristram C, McIntosh G, Rees M, Bench A, et al. Phospho-STAT5 and phospho-Akt expression in chronic myeloproliferative neoplasms. Br J Haematol. 2009;147:495-506 pubmed publisher
    ..Immunocytochemistry of bone marrow trephines for these phospho-proteins can be used as a supplementary diagnostic test with a high negative predictive value...
  62. Hexner E, Serdikoff C, Jan M, Swider C, Robinson C, Yang S, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood. 2008;111:5663-71 pubmed
    Recent studies have demonstrated that patients with myeloproliferative disorders (MPDs) frequently have acquired activating mutations in the JAK2 tyrosine kinase...
  63. Kiladjian J, Cervantes F, Leebeek F, Marzac C, Cassinat B, Chevret S, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008;111:4922-9 pubmed publisher
    ..Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome...
  64. Lasho T, Tefferi A, Hood J, Verstovsek S, Gilliland D, Pardanani A. TG101348, a JAK2-selective antagonist, inhibits primary hematopoietic cells derived from myeloproliferative disorder patients with JAK2V617F, MPLW515K or JAK2 exon 12 mutations as well as mutation negative patients. Leukemia. 2008;22:1790-2 pubmed publisher
  65. Marty C, Lacout C, Martin A, Hasan S, Jacquot S, Birling M, et al. Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. Blood. 2010;116:783-7 pubmed publisher
    ..In conclusion, constitutive heterozygous expression of JAK2(V617F) in mice is not embryo-lethal but results in severe PV-like disease with secondary myelofibrosis and not in ET-like disease as expected from patient study...
  66. Levine R, Gilliland D. Myeloproliferative disorders. Blood. 2008;112:2190-8 pubmed publisher
    ..vera (PV), essential thombocytosis (ET), and primary myelofibrosis (PMF) as pathogenetically related myeloproliferative disorders (MPD)...
  67. Kotecha N, Flores N, Irish J, Simonds E, Sakai D, Archambeault S, et al. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell. 2008;14:335-43 pubmed publisher
    Progress in understanding the molecular pathogenesis of human myeloproliferative disorders (MPDs) has led to guidelines incorporating genetic assays with histopathology during diagnosis...
  68. Stein B, Williams D, Wang N, Rogers O, Isaacs M, Pemmaraju N, et al. Sex differences in the JAK2 V617F allele burden in chronic myeloproliferative disorders. Haematologica. 2010;95:1090-7 pubmed publisher
    ..Since variability in the JAK2(V617F) allele burden is partly responsible for the distinct phenotypes seen in the myeloproliferative disorders, the objective of this study was to identify modifiers of the allele burden.
  69. Wernig G, Gonneville J, Crowley B, Rodrigues M, Reddy M, Hudon H, et al. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes. Blood. 2008;111:3751-9 pubmed publisher
    The V617F activating point mutation in Jak2 is associated with a proportion of myeloproliferative disorders. In normal hematopoietic cells, Jak2 signals only when associated with a growth factor receptor, such as the erythropoietin ..
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    The myeloproliferative disorders are clonal disorders with frequent somatic gain-of-function alterations affecting tyrosine kinases. In these diseases, there is an increase in DNA damage and a risk of progression to acute leukemia...
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    ..However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation...