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Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features

Leukemia volume 20, pages 1641–1644 (2006)Cite this article

Refractory anemia with ringed sideroblasts (RARS) associated with marked thrombocytosis (RARS-T) has clinical and pathologic features of both RARS and essential thrombocytosis (ET). It has been uncertain whether this disease represents a variant of RARS, a variant of ET, or the simultaneous occurrence of two separate disorders (RARS and ET). The recently adopted World Health Organization (WHO) Classification of Hematopoietic and Lymphoid Neoplasms recognized a category of myelodysplastic syndrome/myeloproliferative diseases (MDS/MPD) with clinical, laboratory and morphologic features of both MDS and MPD. RARS-T has been assigned to the MDS/MPD-unclassifiable (MDS/MPD-U) subcategory as a provisional diagnosis in the new WHO classification scheme. A more definitive understanding of the pathogenesis of this syndrome may provide useful prognostic information and suggest potential therapeutic approaches to these patients.

The V617F-activating mutation in the janus kinase 2 (JAK2) tyrosine kinase appears to be a critical event associated with the pathogenesis of most BCR/ABL-negative MPD.1, 2 This mutation has been found in 65–97% of patients with polycythemia vera, 23–57% patients with essential thrombocythemia (ET) and 35–50% patients with primary myelofibrosis (MF). In mouse models, JAK2 V617F mutation can lead to constitutive activation of signal transducers and activators of transcription 5, cytokine-independent growth of colony-forming units-erythroid (CFU-E) and erythropoietin hypersensitivity resulting in erythrocytosis.1 Recently, Steensma et al.3 reported that the V617F JAK2 mutation is an infrequent event in MDS or CMML, with a frequency of 5% (3/119) and 3% (5/101), respectively. The rarity of the V617F JAK2 mutation in MDS has also been noted by several other groups.4, 5

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Acknowledgements

We thank Nancy Lee Harris, MD at MGH, Harvard Medical School, for her valuable comments on WHO hematological malignancy classification. We also thank Jon Iafrate, MD at MGH, Harvard Medical School, for his technical support in JAK2 V617F mutation analysis.

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Authors and Affiliations

  1. Department of Pathology, University of Massachusetts Medical Center, Worcester, MA, USA

    S A Wang, S Hao & B Woda

  2. Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    R P Hasserjian

  3. Department of Pathology, RUSH University Medical School, Chicago, IL, USA

    J M Loew

  4. Department of Medicine, University of Massachusetts Medical Center, Worcester, MA, USA

    E V Sechman, M Mehdi, N Galili & A Raza

  5. Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Huston, TX, USA

    D Jones & W Zhao

  6. Department of Cancer Biology, University of Massachusetts Medical Center, Worcester, MA, USA

    Q Liu

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Correspondence to S A Wang.

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Wang, S., Hasserjian, R., Loew, J. et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features. Leukemia 20, 1641–1644 (2006). https://doi.org/10.1038/sj.leu.2404316

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