NDLI: p90RSK2 is essential for FLT3-ITD– but dispensable for BCR-ABL

Content Provider	PubMed Central
Author	Shannon, Elf Blevins, Dean Jin, Lingtao Chung, Tae-wook Williams, Ifor R. Lee, Benjamin H. Lin, Jian-xin Leonard, Warren J. Taunton, Jack Khoury, Hanna J. Kang, Sumin
Copyright Year	2011
Abstract	p90 ribosomal S6 kinase 2 (p90RSK2) is important in diverse cellular processes including gene expression, cell proliferation, and survival. We found that p90RSK2 is commonly activated in diverse leukemia cell lines expressing different leukemogenic tyrosine kinases, including BCR-ABL and FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD). Interestingly, in a murine BM transplantation (BMT) model, genetic deficiency of RSK2 did not affect the pathogenesis or disease progression of BCR-ABL–induced myeloproliferative neoplasm (PN). In contrast, FLT3-ITD induced a T-cell acute lymphoblastic leukemia in BMT mice receiving RSK2 knockout (KO) BM cells, phenotypically distinct from the myeloproliferative neoplasm induced by FLT3-ITD using wild-type BM cells. In consonance with these results, inhibition of RSK2 by an RSK inhibitor, fmk, did not effectively induce apoptosis in BCR-ABL–expressing murine Ba/F3 cells, human K562 cells or primary tissue samples from CML patients, whereas fmk treatment induced significant apoptotic cell death not only in FLT3-ITD–positive Ba/F3 cells, human Molm14 and Mv(4;11) leukemia cells, but also in primary tissue samples from AML patients. These results suggest that RSK2 is dispensable for BCR-ABL–induced myeloid leukemia, but may be required for pathogenesis and lineage determination in FLT3-ITD–induced hematopoietic transformation. RSK2 may thus represent an alternative therapeutic target in the treatment of FLT3-ITD–positive leukemia.
Related Links	http://dx.doi.org/10.1182/blood-2010-10-315721
Ending Page	6894
Page Count	10
Starting Page	6885
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	25
Volume Number	117
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-06-23
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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