@article{5ca8909f21734351a93fa254708f8f7e,
title = "Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease",
abstract = "Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease phenotype is associated with severely diminished p210-BCR-ABL-induced downstream signaling in primary hematopoietic cells. We utilize NSC23766, a small molecule antagonist of Rac activation, to validate biochemically and functionally Rac as a molecular target in both a relevant animal model and in primary human CML cells in vitro and in a xenograft model in vivo, including in Imatinib-resistant p210-BCR-ABL disease. These data demonstrate that Rac is an additional therapeutic target in p210-BCR-ABL-mediated MPD.",
keywords = "CELLCYCLE",
author = "Thomas, {Emily K.} and Cancelas, {Jose A.} and Chae, {Hee Don} and Cox, {Adrienne D.} and Keller, {Patricia J.} and Danilo Perrotti and Paolo Neviani and Druker, {Brian J.} and Setchell, {Kenneth D.R.} and Yi Zheng and Harris, {Chad E.} and Williams, {David A.}",
note = "Funding Information: Supported by National Institute of Health grant numbers HL69974 and DK62757 (D.A.W.), Leukemia Lymphoma Society grant 6152-06 (D.A.W.), T32 HD046387 (E.K.T.), and Department of Defense New Investigator Award CM064050 (J.A.C). The authors would like to thank Marie-Dominique Filippi, Mick Milsom, and Yi Gu for critical review of the manuscript; David Witte for assistance in the histologic analysis of organs; Jeff Bailey, Victoria Summey, Shelli Homan, Christina Sexton, Caleb Crump, Brian Wolfe, and Andrew Lee for technical assistance; Kara Johnson for coordination of shipments of human specimens; the Division of Experimental Hematology Translational Trials Development and Support Laboratory (Todd Schuesler) for LAM-PCR; and the Flow Cytometry Core Facility at CCHMC for services. ",
year = "2007",
month = nov,
day = "13",
doi = "10.1016/j.ccr.2007.10.015",
language = "English (US)",
volume = "12",
pages = "467--478",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}