1. BCR-JAK2 drives a myeloproliferative neoplasm in transplanted mice
- Author
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Rocío Baños, Elena Almarza, Miguel Ángel Martín-Rey, Elena Fernández-Ruiz, Irene Bodega-Mayor, Paloma Martín-Acosta, Lara Álvarez, Matilde Santos-Roncero, María Luisa Gaspar, Juan A. Bueren, Paula Río, Álvaro Cuesta-Domínguez, Begoña Díez, and Diego Leon-Rico
- Subjects
Myeloid ,breakpoint cluster region ,PIM1 ,Myeloid leukemia ,Biology ,medicine.disease ,Philadelphia chromosome ,Pathology and Forensic Medicine ,Leukemia ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Immunology ,medicine ,Cancer research ,Myeloproliferative neoplasm ,Chronic myelogenous leukemia - Abstract
BCR-JAK2 is an infrequent gene fusion found in chronic/acute, myeloid/lymphoid Philadelphia chromosome-negative leukaemia. In this study, we demonstrated that in vivo expression of BCR-JAK2 in mice induces neoplasia, with fatal consequences. Transplantation of BCR-JAK2 bone marrow progenitors promoted splenomegaly, with megakaryocyte infiltration and elevated leukocytosis of myeloid origin. Analysis of peripheral blood revealed the presence of immature myeloid cells, platelet aggregates and ineffective erythropoiesis. A possible molecular mechanism for these observations involved inhibition of apoptosis by deregulated expression of the anti-apoptotic mediator Bcl-xL and the serine/threonine kinase Pim1. Together, these data provide a suitable in vivo molecular mechanism for leukaemia induction by BCR-JAK2 that validates the use of this model as a relevant preclinical tool for the design of new targeted therapies in Philadelphia chromosome-negative leukaemia involving BCR-JAK2-driven activation of the JAK2 pathway.
- Published
- 2015
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