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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 volume 22, pages 1295–1298 (2008)Cite this article

Myelodysplastic/myeloproliferative disease-unclassifiable (MDS/MPD-U) is a newly defined clinical entity in the World Health Organization (WHO) classification.1 It includes cases with features of both myelodysplasia and myeloproliferation that do not meet the criteria for any of the other MDS or MPD entities. In addition, it includes a provisional subentity refractory anemia with ringed sideroblasts and marked thrombocytosis (RARS-T). Recent studies have shown an increased incidence of JAK2 V617F mutation in patients with RARS-T, suggesting a different biological behavior.2, 3, 4, 5 Our aim was to describe the clinical outcome of MDS/MPD-U patients and, in particular RARS-T patients, who harbor the JAK2 V617F mutation. To identify patients with MDS/MPD-U and RARS-T, we reviewed all patients in the database of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, seen initially between September 1987 and July 2006, with a recorded diagnosis of either MDS/MPD, chronic myeloproliferative disease-unclassifiable or refractory anemia with ringed sideroblasts (RARS) that had platelets>600 × 109 l−1. All cases were reviewed independently by two expert hematopathologists and diagnoses were modified, when appropriate, according to the WHO criteria. The diagnosis of MDS/MPD-U was considered if the case had clinical, laboratory and morphological features of MDS (including erythroid dysplasia) with <20% blasts in the blood and bone marrow, with no history of MDS or MPD, with prominent MPD features (for example, platelets>600 × 109 l−1 or WBC>13 × 109 l−1, with or without splenomegaly), no recent cytotoxic therapy or growth factor use, no del(5q), t(3;3)(q21;q26) or inv(3)(q21q26) cytogenetic abnormalities, or the case had mixed MDS and MPD features but could not be assigned to any other category. To be further subclassified as RARS-T, the case had to include refractory anemia, ringed sideroblasts and platelets>600 × 109 l−1. For the purpose of this study, therefore, the term ‘MDS/MPD-U’ refers to patients with the diagnosis of MDS/MPD-U that do not belong to the subtype RARS-T (they are evaluated separately).

This study was approved by the Institutional Review Board. JAK2 V617F mutational status was assessed using standard PCR technique, using DNA extracted from paraffin-embedded bone marrow core biopsies. Primers included JAK2-Exon14-F (5′-GGACCAAAGCACATTGTATCCTC-3′) and JAK2-Exon14-R (5′-GGGCATTGTAACCTTCTACTT). The resulting 400 bp JAK2 PCR product was purified using the Qiagen PCR Purification Kit (Qiagen, Valencia, CA, USA). Quantitative allele-specific suppressive PCR (ASS-PCR) was then performed using the purified 400 bp PCR product on a sequence detection system 7000 platform (Applied Biosystems, Foster City, CA, USA), as previously described.6 Survival was analyzed by the Kaplan–Meier method and compared using the log-rank test. Categorical values were compared using Pearson's χ2 test.

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Authors and Affiliations

  1. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    E Atallah, R Nussenzveig, C Tam, T Manshouri, S Pierce, H Kantarjian & S Verstovsek

  2. Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C C Yin & C Bueso-Ramos

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  1. E Atallah
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  2. R Nussenzveig
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  3. C C Yin
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Correspondence to S Verstovsek.

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Atallah, E., Nussenzveig, R., Yin, C. 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 22, 1295–1298 (2008). https://doi.org/10.1038/sj.leu.2405054

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