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Identification of a novel TEL–Lyn fusion gene in primary myelofibrosis

Leukemia volume 24, pages 197–200 (2010)Cite this article

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases characterized by an excessive production of blood cells by hematopoietic precursors and are often accompanied by myelofibrosis. The V617F somatic mutation in the Janus kinase 2 gene (JAK2) has recently been found in the majority of patients with polycythemia vera, in 60–70% of patients with essential thrombocythemia and in approximately 50% of patients with primary myelofibrosis (PMF).1 The expression of JAK2 V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow (BM) transplant model.2 In addition, a gain-of-function c-MPL W515 mutation was described in nearly 10% of patients with JAK2 V617F-negative PMF. However, the mechanism responsible for MPN and for the formation of myelofibrosis in patients without the JAK2 or c-MPL mutation is still unclear.

The TEL gene is a member of the ets family transcription factor located on the 12p13 chromosome. It is well known that TEL forms fusion genes with more than 20 partner genes in hematological and even nonhematological malignancies.3 A major group of TEL fusion partners includes protein tyrosine kinases (PTK) and transcriptional factors such as RUNX1 (AML1) in childhood leukemia. The former group includes fusions of TEL to ABL, ARG, JAK2, NTRK3, FGFR3, PDGFR-α and Syk kinase, which have been found in MPN and other hematological malignancies. The most precisely defined mechanism of transformation by TEL–PTK fusion products is through a constitutive kinase activation by oligomerization of TEL–PTK mediated by the PNT domain of TEL in TEL–PTK chimeras.

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  1. H Tanaka and M Takeuchi: These authors contributed equally to this study.

Authors and Affiliations

  1. Division of Hematology, Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan

    H Tanaka, M Takeuchi, Y Takeda, S Sakai, D Abe, C Ohwada, E Sakaida, N Shimizu, Y Saito & C Nakaseko

  2. Department of Cellular and Molecular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan

    M Takeuchi, S Miyagi & A Iwama

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  1. H Tanaka
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Correspondence to C Nakaseko.

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Tanaka, H., Takeuchi, M., Takeda, Y. et al. Identification of a novel TEL–Lyn fusion gene in primary myelofibrosis. Leukemia 24, 197–200 (2010). https://doi.org/10.1038/leu.2009.167

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