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Evidence suggesting the presence of a stem cell clone anteceding the acquisition of the JAK2-V617F mutation

Leukemia volume 22, pages 1472–1474 (2008)Cite this article

The JAK2-V617F mutation is mostly found in classic Philadelphia–chromosome negative myeloproliferative diseases, such as polycythemia vera, essential thrombocytosis (ET) and myeloid metaplasia/myelofibrosis. However, it remains unclear whether the JAK2-V617F mutation is the essential and sufficient molecular event leading to myeloproliferative disease (MPD). Several observations tend to support the existence of a pre-JAK2 mutated clone: (i) the diversity of hematological phenotypes associated with the mutation, which contrasts with the stereotyped phenotype of Philadelphia–positive chronic myelogenous leukemia, (ii) familial cases of MPDs where the JAK2-V617F mutation is thought to be an event occurring on a background of already clonal hematopoiesis or on a germline mutated cell predisposed to acquire new somatic mutations1, 2 and (iii) clonality studies in cohorts of JAK2-V617F-positive MPDs.3, 4 Furthermore, the fact that the leukemic blasts of acute myeloid leukemia (AML) derived from JAK2-V617F-positive MPDs are often negative for the mutation5, 6 raises the question whether MPD and AML arise from two different progenitor cells or are derived from a common ancestor in which the JAK2-V617F mutation is a late event leading to MPD.

Here, we describe the unusual case of a patient diagnosed with de novo AML in which the allogeneic transplantation setting allowed for the unique observation of the sequence of events leading to the acquisition of the JAK2-V617F mutation, and the possible multistep pathogenesis underlying the development of secondary AML derived from a preexisting MPD.

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Authors and Affiliations

  1. Department of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Canada

    R Jamal, M-C Lessard, J Hébert, D-C Roy & L Busque

  2. Research Centre, Maisonneuve-Rosemont Hospital, Montreal, Canada

    C Bélisle, J Hébert, D-C Roy & L Busque

  3. Faculty of Medicine, University of Montreal, Montreal, Canada

    J Hébert, D-C Roy & L Busque

  4. Québec Leukemia Cell Bank, University of Montreal, Montreal, Canada

    J Hébert

  5. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    R Levine

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  1. R Jamal
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  2. C Bélisle
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Correspondence to L Busque.

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Jamal, R., Bélisle, C., Lessard, MC. et al. Evidence suggesting the presence of a stem cell clone anteceding the acquisition of the JAK2-V617F mutation. Leukemia 22, 1472–1474 (2008). https://doi.org/10.1038/leu.2008.6

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