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BCR–JAK2 drives a myeloproliferative neoplasm in transplanted mice
Author(s) -
CuestaDomínguez Álvaro,
LeónRico Diego,
Álvarez Lara,
Díez Begoña,
BodegaMayor Irene,
Baños Rocío,
MartínRey Miguel Ángel,
SantosRoncero Matilde,
Gaspar María Luisa,
MartínAcosta Paloma,
Almarza Elena,
Bueren Juan A.,
Río Paula,
FernándezRuiz Elena
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4513
Subject(s) - myeloproliferative neoplasm , breakpoint cluster region , neoplasm , myeloproliferative disorders , cancer research , myelofibrosis , medicine , pathology , bone marrow , receptor
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. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.