New SRC/ABL inhibitors for chronic myeloid leukemia therapy show selectivity for T315I ABL mutant CD34+ cells

Imatinib mesylate (IM, formerly STI571 or Glevec), a tyrosine kinase (TK) inhibitor which selectively targets ATP-binding sites of ABL and BCR-ABL proteins, is the frontline treatment of chronic myeloid leukemia (CML). The major caveat of IM therapy in CML is the development of secondary resistance (defined as loss of drug response with estimated disease relapse rates and progression of 17% and 7% respectively) most frequently due to point mutations of BCR-ABL that interfere with drug binding to p210 kDa protein.