BCR-JAK2 drives a myeloproliferative neoplasm in transplanted mice
| Autor: | Álvaro, Cuesta-Domínguez, Diego, León-Rico, Lara, Álvarez, Begoña, Díez, Irene, Bodega-Mayor, Rocío, Baños, Miguel Ángel, Martín-Rey, Matilde, Santos-Roncero, María Luisa, Gaspar, Paloma, Martín-Acosta, Elena, Almarza, Juan A, Bueren, Paula, Río, Elena, Fernández-Ruiz |
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| Rok vydání: | 2014 |
| Předmět: |
Gene Rearrangement
Male Mice Inbred BALB C Leukocytosis Hematopoietic Stem Cell Transplantation Janus Kinase 2 Hematopoietic Stem Cells Leukemia Myeloid Chronic Atypical BCR-ABL Negative Retroviridae Transduction Genetic Proto-Oncogene Proteins c-bcr Splenomegaly STAT5 Transcription Factor Animals Female Transgenes Neoplasm Transplantation |
| Zdroj: | The Journal of pathology. 236(2) |
| ISSN: | 1096-9896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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