AI Article Synopsis
- BCR-JAK2 is a rare gene fusion linked to various types of leukemia that do not involve the Philadelphia chromosome; this study shows that its expression in mice causes severe cancer development.
- Transplanting bone marrow with BCR-JAK2 leads to enlarged spleens, excessive white blood cells, and the presence of immature myeloid cells in the blood, indicating serious blood-related issues.
- The findings suggest that BCR-JAK2 promotes leukemia by disrupting normal cell death processes, which may help in creating new targeted treatments for Philadelphia chromosome-negative leukemia.
Article 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.
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| http://dx.doi.org/10.1002/path.4513 | DOI Listing |
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