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Acute Leukemias

JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained

Leukemia volume 20, pages 971–978 (2006)Cite this article

Abstract

Signal transducer and activator of transcription (STAT) proteins are phosphorylated and activated by Janus kinases (JAKs). Recently, several groups identified a recurrent somatic point mutation constitutively activating the hematopoietic growth factor receptor-associated JAK2 tyrosine kinase in diverse chronic myeloid disorders – most commonly classic myeloproliferative disorders (MPD), especially polycythemia vera. We hypothesized that the JAK2 V617F mutation might also be present in samples from patients with acute myeloid leukemia (AML), especially erythroleukemia (AML-M6) or megakaryoblastic leukemia (AML-M7), where it might mimic erythropoietin or thrombopoietin signaling. First, we documented STAT3 activation by immunoblotting in AML-M6 and other AML subtypes. Immunoperoxidase staining confirmed phosphorylated STAT3 in malignant myeloblasts (21% of cases, including all AML-M3 samples tested). We then analyzed genomic DNA from 162 AML, 30 B-cell lymphoma, and 10 chronic lymphocytic leukemia (CLL) samples for JAK2 mutations, and assayed a subset for SOCS1 and FLT3 mutations. Janus kinase2 V617F was present in 13/162 AML samples (8%): 10/13 transformed MPD, and three apparent de novo AML (one of 12 AML-M6, one of 24 AML-M7, and one AML-M2 – all mixed clonality). FLT3 mutations were present in 5/32 (16%), while SOCS1 mutations were totally absent. Lymphoproliferative disorder samples were both JAK2 and SOCS1 wild type. Thus, while JAK2 V617F is uncommon in de novo AML and probably does not occur in lymphoid malignancy, unexplained STAT3 activation is common in AML. Janus kinase2 extrinsic regulators and other proteins in the JAK-STAT pathway should be interrogated to explain frequent STAT activation in AML.

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Acknowledgements

We thank Nga T Dai and David A Loegering for assistance with immunoblotting. This project was funded by National Cancer Institute grants K12 CA90628 to DPS, R01 CA69008 to SHK, and P50 CA97274 (Mayo Clinic/University of Iowa Lymphoma Specialized Program of Research Excellence), and by a grant from the Robert A Kyle Hematological Malignancies Program to DPS. The authors have no potential conflicts of intrest to report.

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  1. Mayo Clinic College of Medicine, Rochester, MN, USA

    D P Steensma, R F McClure, A Tefferi, T L Lasho, H L Powell, G W DeWald & S H Kaufmann

  2. Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD, USA

    J E Karp

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  1. D P Steensma
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  2. R F McClure
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Correspondence to D P Steensma.

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Steensma, D., McClure, R., Karp, J. et al. JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained. Leukemia 20, 971–978 (2006). https://doi.org/10.1038/sj.leu.2404206

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