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Transformed essential thrombocytosis with a JAK2 V617F mutation relapsing as JAK2 mutation-negative leukaemia after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 38, pages 573–574 (2006)Cite this article

The finding of a single mutation in the JH2 auto-inhibitory domain of the JAK2 kinase (V617F) in a wide variety of myeloproliferative diseases (MPD) has revolutionized their definition.1 The mutation is present in erythroblasts, granulocytes, platelets and multipotent haematopoietic progenitors.2 The JAK2 mutation has a potential role for the monitoring of residual disease after haematopoietic stem cell transplantation (HSCT) for MPD.

In a prospective study using real-time PCR in HSCT recipients, Elmaagacli et al.5 detected the JAK2 mutation in 15 of 35 (42%) MPD cases, but not in acute myeloid leukaemia or myelodysplasia (n=61). In 11 of these 15 cases, achievement of complete donor chimerism was associated with eradication of the JAK2 clone. In three patients, persistence of JAK2 mutation and mixed chimerism heralded disease relapse. Interestingly, in one remaining case, mixed chimerism between donor and recipient JAK2 mutation negative haematopoiesis was reported.5 In our case, the neoplastic clone with V617F mutation was eradicated after HSCT. However, autologous marrow regeneration and the emergence of a neoplastic clone with germline JAK2 status ultimately led to leukaemia relapse. In ET patients, non-V617F related progenitors are known to coexist in variable proportions. Despite the long clinical course culminating in leukaemic transformation in our patient, residual haematopoiesis without V617F still existed at the time of conditioning, and was preferentially selected for after HSCT. It is uncertain whether the leukaemic clone before HSCT was actually V617F negative, or whether the post-HSCT leukaemia was a separate event. The long latency between autologous regeneration and frank leukaemia suggested the latter case. Parallel transformation of non-leukaemic precursors have been reported to complicate HSCT, and may be induced by hydroxyurea, HSCT conditioning or azathioprine.4 On the other hand, recent data suggested V617F negative leukaemia may not be an uncommon event in transformed V617F positive ET patients, suggesting the former scenario.6 In either case, this presents a potential pitfall to the use of JAK2 mutation for minimal residual disease monitoring after HSCT.

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References

  1. Tefferi A, Gilliland DG . JAK2 in myeloproliferative disorders is not just another kinase. Cell Cycle 2005; 4: 1053–1056. (E-pub ahead of print 2005 August 26).

    Article  CAS  Google Scholar 

  2. Goerttler PS, Steimle C, Marz E, Johansson PL, Andreasson B, Griesshammer M et al. The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients. Blood 2005; 106: 2862–2864.

    Article  CAS  Google Scholar 

  3. Au WY, Fung A, Liu CL, Fan ST, Kwong YL . Serial analysis of Jak2 mutation in a patient who develop essential thrombocythemia after orthotopic liver transplantation. Am J Hematol 2006 (in press).

  4. Au WY, Lie AK, Ma SK, Leung YH, Siu LL, Kwong YL . Therapy-related myelodysplastic syndrome of recipient origin after allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Br J Haematol 2001; 112: 424–426.

    Article  CAS  Google Scholar 

  5. Elmaagacli AH, Steckel NK, Koldehoff M, Ditschkowski M, Trenschel R, Beelen DW . Detection of the acquired tyrosine kinase JAK2 gene mutation by real time PCR as minimal residual disease marker for patients after allogeneic hematopoetic stem cell transplantation. Blood 2005; 106: 1212.

    Google Scholar 

  6. Campbell PJ, Baxter EJ, Beer PA, Scott LM, Bench AJ, Huntly BJ et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations and role in leukemic transformation. Blood 2006 (E-pub ahead of print July 27).

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  1. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, Hong Kong

    W Y Au, A Fung, K Y Lam, A K Lie, R Liang & Y L Kwong

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  1. W Y Au
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Correspondence to W Y Au.

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Au, W., Fung, A., Lam, K. et al. Transformed essential thrombocytosis with a JAK2 V617F mutation relapsing as JAK2 mutation-negative leukaemia after allogeneic stem cell transplantation. Bone Marrow Transplant 38, 573–574 (2006). https://doi.org/10.1038/sj.bmt.1705482

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