Our observation that inhibition of BCR-ABL or TEL-ABL resulted in dephosphorylation of the S6 protein in only 3 of 7 cases (2/6 BCR-ABL, 1/1 TEL-ABL), and that the extent of imatinib-induced S6 dephosphorylation does not correlate with the sensitivity of the BCR-ABL+ ALL-LTCs to imatinib, point to an unexpected heterogeneity in mechanisms of TKI-induced inhibition. The gene discussed is RPS6; the disease is acute lymphoblastic leukemia.