Low expression of Abelson interactor-1 is linked to acquired drug resistance in Bcr-Abl-induced leukemia.

ABSTRACT: The basis for persistence of leukemic stem cells in the bone marrow microenvironment remains poorly understood. We present evidence that signaling cross-talk between ?4 integrin and Abelson interactor-1 (Abi-1) is involved in the acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl-positive leukemia cells. Comparison of Abi-1 (ABI-1) and ?4 integrin (ITGA4) gene expression in relapsing Bcr-Abl-positive CD34+progenitor cells demonstrated a reduction in Abi-1 and an increase in ?4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and ?4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate -resistant leukemic cells. These results indicate that the ?4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells.

SUBMITTER: Chorzalska A 

PROVIDER: S-EPMC4185277 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature