Expression of TEL-JAK2 in primary human hematopoietic cells drives erythropoietin-independent erythropoiesis and induces myelofibrosis in vivo.

ABSTRACT: Activation of JAK2 by chromosomal translocation or point mutation is a recurrent event in hematopoietic malignancies, including acute leukemias and myeloproliferative disorders. Although the effects of activated JAK2 signaling have been examined in cell lines and murine models, the functional consequences of deregulated JAK2 in the context of human hematopoietic cells are currently unknown. Here we report that expression of TEL-JAK2, a constitutively active variant of the JAK2 kinase, in lineage-depleted human umbilical cord blood cells results in erythropoietin-independent erythroid differentiation in vitro and induces the rapid development of myelofibrosis in an in vivo NOD/SCID xenotransplantation assay. These studies provide functional evidence that activated JAK2 signaling in primitiv

SUBMITTER: Kennedy JA 

PROVIDER: S-EPMC1629449 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature