GM-CSF expression in primary CML samples. (A) GMCSF mRNA expression was quantitated relative to GAPDH expression in 52 patients with chronic-phase CML at diagnosis and 29 patients with CML at the time of clinically manifested IM resistance. The cell sources of mRNA (bone marrow, peripheral blood, or PBMCs) are indicated. *Presence of a BCR/ABL kinase mutation at the time of IM resistance. – indicates no available kinase mutation analysis; #, patient no. 1 (PBMCs). (B) GM-CSF ELISA. The GM-CSF concentration was determined in whole peripheral blood cell lysates of IM-sensitive patients with first-diagnosis CML and IM-resistant patients with CML. Bars represent means of duplicate measurements ± SD; **P = .006 (Mann-Whitney test). BCR/ABL kinase mutations are shown; # indicates patient no.1 (Table S1). (C) Different mechanisms of IM/NI resistance on the progenitor and stem cell compartment. Autocrine or paracrine secretion of GM-CSF stimulates BCR/ABL-independent growth and survival of GMPs.