title: The emerging role of Bcr-Abl-induced cystoskeletal remodeling in systemic persistence of leukemic stem cells.
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.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bartos
authors.affiliation: Signal Transduction Lab., Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Patrycja_Dubielecka-Szczerba@brown.edu.
authors.forename: Patrycja M
authors.initials: PM
authors.lastname: Dubielecka
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D016044:Fusion Proteins, bcr-abl