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The Emerging Role of Bcr-Abl-Induced Cystoskeletal Remodeling in Systemic Persistence of Leukemic Stem Cells

[ Vol. 11 , Issue. 5 ]

Author(s):

Adrian Bartos and Patrycja M. Dubielecka   Pages 582 - 591 ( 10 )

Abstract:


Abl kinase plays a critical role in development and homeostasis of hematopoietic system. The importance of this kinase becomes apparent from the consequences of a specific, reciprocal translocation between chromosome 9 and chromosome 22 that yields a chimeric fusion protein, Bcr-Abl, in which the function of auto-regulatory mechanisms are inactivated. The resultant constitutively active kinase is responsible for development of a systemic leukemogenic phenotype. Studies employing currently available highly specific inhibitors, with high potency to block kinase activity, uncovered unanticipated characteristics of Bcr-Abl fusion protein. It became apparent that the kinase domain, with its primary significance for development and progression of leukemia, is not solely responsible for leukemogenic features of the Bcr-Abl transformed leukemic stem cells. In this review we summarize current understanding of non-enzymatic characteristics of Bcr-Abl, its effect on actin cytoskeleton, and its potential contribution to drug resistance and systemic persistence of leukemic stem cells.

Keywords:

Actin cytoskeleton, Imatinib mesylate, Leukemic stem cells, Rho GTPases.

Affiliation:

Signal Transduction Lab., Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.

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