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Newly described activating JAK3 mutations in T-cell acute lymphoblastic leukemia

Leukemia volume 26, pages 2144–2146 (2012)Cite this article

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T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that accounts for 10–15% of adult and 25% of childhood ALL cases. Despite advances in therapy of T-ALL, relapsed disease remains a leading cause of death. The genetic and biological determinants of treatment failure and clinical outcomes remain incompletely understood.

The JAK/STAT signaling cascade is essential in hematopoiesis, and somatic mutations of JAK1, JAK2 and JAK3 have been reported in a wide variety of hematological disorders. JAK1 mutations occur in nearly 20% of T-ALL cases and at a lower frequency in B-cell ALL (B-ALL).1 In addition to the JAK2 V617F mutation, the most common mutation in myeloproliferative neoplasms, other JAK2 mutations have been reported in 10% of pediatric high-risk B-cell ALL2 and 20% of Down Syndrome ALL.3 Jeong et al.4 screened 494 acute leukemias and solid tumors and identified JAK1 mutation as a frequent event in T-ALL (3/11), whereas JAK3 mutations were only found in breast and gastric carcinoma. JAK3 mutations have been reported in a small number of hematopoietic neoplasms, including adult T-cell leukemia/lymphoma,5 cutaneous T-cell lymphoma6 and acute megakaryoblastic leukemia.7 However, there have been no published data reporting JAK3 mutations in T-ALL.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Oregon Health & Science University, Portland, OR, USA

    T Bains, M C Heinrich & C Beadling

  2. Department of Hematology and Oncology, VA Medical Center, Portland, OR, USA

    M C Heinrich & C Beadling

  3. Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    M C Heinrich, M M Loriaux, C Beadling, D Nelson, A Warrick, T L Neff, J W Tyner, J Dunlap, C L Corless & G Fan

  4. Department of Pathology, Oregon Health & Science University, Portland, OR, USA

    M M Loriaux, J Dunlap, C L Corless & G Fan

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  1. T Bains
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Correspondence to G Fan.

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Michael Heinrich has equity interest in and is a consultant for Molecular MD. The other authors declare no conflict of interest.

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Bains, T., Heinrich, M., Loriaux, M. et al. Newly described activating JAK3 mutations in T-cell acute lymphoblastic leukemia. Leukemia 26, 2144–2146 (2012). https://doi.org/10.1038/leu.2012.74

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