Oncogene-independent resistance in Philadelphia chromosome - positive (Ph⁺) acute lymphoblastic leukemia (ALL) is mediated by activation of AKT/mTOR pathway.

ABSTRACT: Tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, dasatinib, and ponatinib have significantly improved the life expectancy of Philadelphia chromosome-positive (Ph⁺) acute lymphocytic leukemia (ALL) patients; however, resistance to TKIs remains a major clinical challenge. Point mutations in the tyrosine kinase domain (TKD) of BCR-ABL1 have emerged as the predominant cause of acquired resistance. In approximately 30% of patients, the mechanism of resistance to TKIs remains elusive. This study aimed to investigate mechanisms of nonmutational resistance in Ph⁺ ALL. Here we report the development of a nonmutational resistance cell line SupB15-RT; conferring resistance to approved ABL kinase inhibitors (AKIs) and allosteric inhibitors GNF-2, ABL001, and crizoti

SUBMITTER: Mian AA 

PROVIDER: S-EPMC8368770 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature