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High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis

Leukemia volume 20, pages 2067–2070 (2006)Cite this article

Activation of tyrosine kinase pathways has been implicated in the pathogenesis of myeloproliferative disorders (MPD). Recently, a point mutation of the cytoplasmic Janus kinase 2 (JAK2) has been identified in MPD, including polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). JAK2 V617F is a somatic mutation present in hematopoietic cells that leads to constitutive activation of the JAK2 tyrosine kinase and phosphorylation of STAT5. Expression of the JAK2 V617F kinase in vitro leads to factor-independent growth.1, 2 In addition, expression of JAK2 V617F in a murine bone marrow transplant model results in erythrocytosis in recipient mice.1 JAK2 V617F mutation was detected by several groups in most PV patients (90%) and in approximately 40% of ET and 50% of IMF patients.1, 2, 3, 4 These data suggest that JAK2 V617F mutation is likely to contribute to the development of MPD and, therefore, may be one diagnostic tool for the identification of MPD. JAK2 V617F mutation also occurs in other myeloid malignancies, such as Philadelphia chromosome-negative chronic myeloid leukemia (atypical CML), chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), but it is relatively infrequent in these diseases compared to the three classic BCR-ABL-negative MPD.5

The recent World Health Organization (WHO) classification recognizes a separated category of myeloid disorders that overlaps traditional MDS and MDP as the entity MDS/MPD. This hybrid group comprises four subtypes: CMML, juvenile myelomonocytic leukemia, atypical CML and unclassifiable MDS/MPD, including MDS with thrombocytosis >600 G/l, common feature of MPD. For this reason, refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) has been categorized as unclassifiable MDS/MPD, until further information is available regarding its pathogenesis.6 Appropriate classification for RARS-T remains a matter of debate.

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Acknowledgements

This work was supported by the Cancéropole Nord-Ouest (Axe Onco-hématologie).

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Authors and Affiliations

  1. Laboratoire d'Hématologie, Hôpital Calmette, CHRU de Lille, Lille, France

    A Renneville, A Crinquette & C Preudhomme

  2. Service des Maladies du Sang, CHRU de Lille, Lille, France

    B Quesnel, L Terriou, P Lionne-Huyghe & F Bauters

  3. INSERM, Unité 817, Institut de Recherche sur le Cancer de Lille, Lille, France

    B Quesnel & C Preudhomme

  4. Laboratoire d'Hématologie, Groupe Hospitalier de l'Institut Catholique Lillois (GHICL), Hôpital Saint-Philibert, Lomme, France

    A Charpentier

  5. Laboratoire d'Hématologie, Centre Hospitalier d'Arras, Arras, France

    A Crinquette

  6. Laboratoire de Cytogénétique, Hôpital Jeanne de Flandres, CHRU de Lille, Lille, France

    J-L Laï

  7. Laboratoire de Cultures Cellulaires, Faculté de Médecine, Pôle Recherche, Lille, France

    C Cossement

  8. Unité d'Hématologie et de Médecine Interne, Centre Hospitalier d'Arras, Arras, France

    P Lionne-Huyghe

  9. Service d'Hématologie,

    C Rose

  10. Groupe Hospitalier de l'Institut Catholique Lillois (GHICL), Hôpital Saint-Vincent, Lille, France

    C Rose

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Renneville, A., Quesnel, B., Charpentier, A. et al. High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Leukemia 20, 2067–2070 (2006). https://doi.org/10.1038/sj.leu.2404405

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