ESTABLISHMENT OF NOVEL CELL-LINES DERIVED FROM 2 PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA IN BLAST CRISIS - IMS-BC1 AND IMS-BC2 WHICH EXHIBIT MARKEDLY DIFFERENT SENSITIVITY TO APOPTOSIS

We established two novel cell lines, designated as IMS-BC1 and IMS-BC2 , from two patients with chronic myelogenous leukemia in blast crisis. The two cell lines were positive for CD13 and CD33 and negative for C D34 and HLA-DR by surface marker analysis. IMS-BC1 had four Philadelph ia (Phl) chromosomes and a breakpoint within the 3'-portion of M-bcr, and IMS-BC2 had five Phl chromosomes and two breakpoints within the 3' - and 5'-portions of M-bcr. Both cell lines' growth activities were mo derately suppressed by IFN-alpha. The proliferation of IMS-BC2 was inh ibited by IFN-gamma and apoptosis was induced within 72 h, while IMS-B C1 was resistant to IFN-gamma. Fibronectin inhibited the proliferation of the two cell lines at higher than 10 mu g/ml, but only IMS-BC2 sho wed apoptosis. Transforming growth factor-beta inhibited the prolifera tion of IMS-BC2 resulting in apoptosis, while it inhibited that of IMS -BC1 moderately but failed to induce apoptosis. All-trans retinoic aci d (ATRA) inhibited the proliferation of IMS-BC2 at very low concentrat ion (10(-17) mol/l) and induced apoptosis at doses higher than 10(-9) mol/l within 72 h without terminal differentiation, while IMS-BC1 was completely resistant to ATRA. The two cell lines showed different resp onses to growth inhibitory cytokines and factors. These cell lines sho uld prove useful in the analysis of mechanisms of apoptosis induced by growth inhibitory cytokines and factors. (C) 1998 Elsevier Science Ir eland Ltd. All rights reserved.