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Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia

Leukemia volume 20, pages 381–383 (2006)Cite this article

Activating mutations in genes encoding for signaling molecules are frequently detected in human malignancies. In acute leukemias these mutations may act as cooperating events conferring a proliferative advantage to hematopoietic progenitors. A number of the same genetic lesions that deregulate proliferation in acute myeloid (AML) and/or lymphoblastic leukemia (ALL) such as activating mutations in RAS and PTPN11 or the BCR/ABL fusions also play integral roles in the pathogenesis of myeloproliferative disorders (MPD).

JAK2 is one of the four mammalian Janus kinases (JAK) that, after activation of cytokine or growth factor receptors, are recruited and activated through trans-phosphorylation. Following their activation, JAK proteins phosphorylate specific tyrosine residues on the receptor, which then bind to signal transducer and activator of transcription (STAT) proteins that further activate downstream signaling events.1 Recently, several groups described a clonal and recurrent mutation, c.1849G>T (V617F), in the pseudo-kinase (JH2)-domain of the JAK2 gene in most patients with polycythemia vera and in a substantial proportion of patients with essential thrombocythemia, and chronic idiopathic myelofibrosis (reviewed in Shannon and Van Etten2). This gain-of-function mutation, which is frequently duplicated by mitotic recombination, predicts to disrupt the auto-inhibition of the catalytic domain by the JH2-domain. The mutation confers cytokine independent growth in vitro and induces erythrocytosis in a murine model (reviewed in Shannon and Van Etten2). In more recent studies, the same somatic mutation has been identified in a small percentage of patients with AML (AML-M7 and AML after MPD), chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, idiopatic hypereosinophilic syndrome, systemic mastocytosis, chronic neutrophilic leukemia and, rarely, in patients with myelodysplastic syndrome.3, 4, 5, 6

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Authors and Affiliations

  1. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany

    C P Kratz, S Böll, U Kontny & C M Niemeyer

  2. Department of Pediatrics, University of Kiel, Kiel, Germany

    M Schrappe

  3. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    M Stanulla

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  1. C P Kratz
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  2. S Böll
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Kratz, C., Böll, S., Kontny, U. et al. Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 20, 381–383 (2006). https://doi.org/10.1038/sj.leu.2404060

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