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Chronic myeloproliferative diseases with concurrent BCR–ABL junction and JAK2V617F mutation

Leukemia volume 22, pages 1059–1062 (2008)Cite this article

Chronic myeloproliferative diseases (CMPDs) are clonal disorders of haematopoietic stem cells and are classified according to their clinical and phenotypical features and genetic aberrations.1 CMPDs are usually divided according to the presence of a Philadelphia chromosome/BCR–ABL fusion (Ph+) as chronic myeloid leukaemia (CML) and the Philadelphia chromosome negative (Ph−) CMPD (polycythaemia vera (PV), essential thrombocythaemia (ET), primary myelofibrosis (PMF)). More than 95% of PV and ∼60% of ET and PMF are positive for the 1849G>T/V617F point mutation of the Janus kinase 2 (JAK2V617F), which is highly specific for Ph−-CMPD.1 Small subfractions of ET and PMF (∼5%) show another gain of function mutation that affects the thrombopoietin receptor (1544G>T/A/W515L/K in the myeloproliferative leukaemia virus oncogene, (MPLW515L/K)).1

A subgroup of Ph+-CML mimics ET or PMF by presenting with marked thrombocytosis or myelofibrosis (MF), but only single cases with concomitant Ph+-CML and Ph−-CMPD were reported so far.2, 3, 4, 5 Recently, our group Inami et al., Krämer et al., and Bornhäuser et al. 2, 3, 4, 5 simultaneously reported on four well-documented cases with concurrent JAK2V617F and BCR–ABL translocation (Table 1). The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission whereas the JAK2V617F clone either persisted or became clinically manifest as PMF2, 3, 4 or PV.5 In our previously reported case, a minor JAK2V617F clone expanded after major response of Ph+-CML to IM.2

Table 1 BCR–ABL and JAK2V617F mutation status, therapy and clinical parameters at presentation and during the course of disease in published cases and all four cases (nos. 1–4) of this series
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Acknowledgements

This work was financially supported by a research grant Deutsche Krebshilfe, Dr Mildred Scheel Stiftung 10-2191 (OB, HK) and Deutsche Forschungsgemeinschaft –DFG BO 1954/1-1 (OB, HK). We wish to thank Ms Sabine Schröter and Ms Susann Kostmann for their skilful work. Furthermore, we thank Dr med Ruthild Grips from the private practice for Haematology and Oncology, Bonn, Germany and Dr med Hans Peter Feustel from the private practice for Haematology and Oncology, Speyer, Germany for their support.

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Authors and Affiliations

  1. Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany

    K Hussein, O Bock, K Theophile, A Seegers, G Büsche & H Kreipe

  2. Institute of Pathology, Klinikum Fulda, Fulda, Germany

    H Arps & O Basten

  3. Private practice for Haematology and Oncology, Bonn, Germany

    K-H Grips

  4. Private practice for Haematology and Oncology, Speyer, Germany

    J Franz-Werner

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  1. K Hussein
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Correspondence to H Kreipe.

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Hussein, K., Bock, O., Theophile, K. et al. Chronic myeloproliferative diseases with concurrent BCR–ABL junction and JAK2V617F mutation. Leukemia 22, 1059–1062 (2008). https://doi.org/10.1038/sj.leu.2404993

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