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The introduction of molecularly targeted drugs in the 21 st century marks an exciting era for cancer therapy.One of the first of these agents is Imatinib (IM,Gleevec),a selective tyrosine kinase inhibitor that blocks the catalytic activity of the BCR-ABL oncoprotein.IM therapy has revolutionized the treatment of Chronic Myeloid Leukemia (CML) worldwide.Nevertheless,early relapses and IM-resistant disease occur in a significant proportion of patients.Relapses are frequently associated with BCR-ABL kinase domain mutations,suggesting that failure of IM therapy to eradicate CML stem cells may underlie the accumulation of mutations.We have recently discovered that FACS purified leukemic stem cells (lin-CD34+CD38-cells) are highly resistant to IM and possess multiple unique features that predict intrinsic and acquired resistance to BCR-ABL-targeted therapeutics.We have now investigated whether any of these parameters were associated subsequent clinical responses to IM therapy in pretreatment CD34+ stem/progenitor cells from 25 patients (11 responders and 14 non-responders).Interestingly,CD34+cells from non-resnonders demonstrated greater resistance to IM in CFC assays (P<0.001) compared to CD34+cells from responders.