Title:The Emerging Role of Bcr-Abl-Induced Cystoskeletal Remodeling in Systemic Persistence of Leukemic Stem Cells
Volume: 11
Issue: 5
Author(s): Adrian Bartos and Patrycja M. Dubielecka
Affiliation:
Keywords:
Actin cytoskeleton, Imatinib mesylate, Leukemic stem cells, Rho GTPases.
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.