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The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis

Leukemia volume 20, page 1165 (2006)Cite this article

We read with interest the letter by Ohyashiki et al.1 describing JAK2 V617F mutation in two of six patients with myelodysplastic syndrome (MDS) developing myelofibrosis. The authors postulated that JAK2 V617F mutation might either be secondarily acquired in MDS, leading to myelofibrosis or alternatively, the two cases were myeloproliferative disorders (MPD) masquerading as MDS. However, owing to the lack of information on the JAK2 mutation status in the pre-fibrotic phase of these cases and a paucity of clinical and hematological data, it was not possible to distinguish between the two clinical scenarios. It is well known that dysplastic features in blood cells can be seen in typical MPD during disease evolution, and studies on myelofibrosis in MDS to date have been criticized for non-uniform and arbitrary selection criteria, resulting in the inclusion of patients having higher level of blood counts and variable degree of splenomegaly,2, 3, 4 some of whom might have been better classified as MPD in transformation.

To assess the occurrence and prevalence of JAK2 V617F mutation in genuine cases of MDS with secondary myelofibrosis, we identified from a cohort of 186 patients with MDS nine cases with secondary fibrosis (4.8%) using a uniform set of criteria proposed by Steenama et al.4 Briefly, all these nine cases demonstrated definite dysplastic features in blood cells, absence of peripheral blood cytosis, no or minimal splenomegaly and absence of clustering of large atypical megakaryocytes. All nine patients had high-grade MDS at the time of development of secondary myelofibrosis. Prognosis of this group was poor. Five patients progressed to acute leukemia (median survival 28 months; median follow-up 20 months, range 6–108 months). The two long-term survivors were allogeneic bone marrow transplant recipients. Six patients had archival samples available for JAK2 V617F mutation analysis by allele-specific PCR.5 None of them were positive. To assess the possibility that JAK2 mutation may precede the onset of fibrosis in MDS, we also analyzed 39 patients with MDS (five with refractory anemia , refractory anaemia with ringed sideroblasts in five, refractory cytopenia with multilineage dysplasia in 13, refractory cytopenia with multilineage dysplasia and ringed sideroblasts in two, refractory anemia with excess blasts-1 in 5, refractory anemia with excess blasts-2 in 3, MDS-unclassifiable in six) and all were found to be negative for JAK2 V617F mutation. As expected, JAK2 V617F mutation analysis performed concurrently in 30 patients with MPD showed similar prevalence of the mutation to published series (detection rate of 43% in essential thrombocythemia (3/7), 56% in chronic idiopathic myelofibrosis (5/9), 100% in polycythemia vera (9/9), 40% in MPD-unclassifiable (2/5)). Our results suggested that JAK2 V617F is unlikely to play a significant role in the pathobiology of MDS, with or without secondary myelofibrosis. We propose that strict clinical and laboratory criteria is required to exclude the more likely diagnosis of MPD in transformation when JAK2 V617F mutation is detected in patients with blood cell dysplasia and myelofibrosis.

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References

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Acknowledgements

We gratefully acknowledge the Department of Medicine, Queen Mary Hospital; Department of Pathology, Princesses Margaret Hospital; Department of Pathology, Pamela Youde Nethersole Eastern Hospital; Department of Pathology, Caritas Medical Centre; Clinical Laboratory, St, Teresa's Hospital and Hong Kong Baptist Hospital Laboratory for patients management and referral.

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Authors and Affiliations

  1. Haematology Division, Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong

    S-F Yip, C-C So, Ay-Y Chan, Ts-K Wan & L-C Chan

  2. Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong

    Hs-Y Liu

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  1. S-F Yip
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Yip, SF., So, CC., Chan, AY. et al. The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis. Leukemia 20, 1165 (2006). https://doi.org/10.1038/sj.leu.2404196

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