PMID- 11368361 OWN - NLM STAT- MEDLINE DCOM- 20010531 LR - 20190915 IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 15 IP - 4 DP - 2001 Apr TI - Effect of a selective Abl tyrosine kinase inhibitor, STI571, on in vitro growth of BCR-ABL-positive acute lymphoblastic leukemia cells. PG - 590-4 AB - By employing a new semi-quantitative assay system that includes co-culturing leukemia cells with the mouse bone marrow-derived stromal cell line MS-5, we examined the suppressive effect of a selective inhibitor of ABL tyrosine kinase, STI571, on acute lymphoblastic leukemia (ALL) cells with BCR-ABL fusion. Leukemic blast cells from eight patients with B-precursor ALL, including three patients with BCR-ABL-positive ALL, were cultured on monolayers of MS-5 cells for 3 weeks with or without addition of variable amounts of STI571. In all cases, cobblestone areas (CAs) were formed, showing clear linear cell dose-dependent curves, allowing quantitative assessment of blast cell growth. The progenitor frequencies obtained by this direct CA-forming cell (CAFC) assay were equivalent to ALL progenitor frequencies assessed by the standard limiting dilution assay. The number of CAFCs ranged from 12.3 to 140.3/10(4) cells. In BCR-ABL-positive ALL patients, CA-containing cells were examined by FISH, and all contained BCR-ABL fusion genes. STI571 inhibited CA formation of BCR-ABL-positive ALL cells virtually 100% at 0.1-1.0 micromol/l. None of the five BCR-ABL-negative ALL patients showed this growth inhibition by STI571 at 0.1-1.0 micromol/l. Our results indicate that STI571 selectively inhibits in vitro growth of BCR-ABL-positive ALL cells. FAU - Kawaguchi, Y AU - Kawaguchi Y AD - Department of Hematology, Nagasaki University School of Medicine, Japan. FAU - Jinnai, I AU - Jinnai I FAU - Nagai, K AU - Nagai K FAU - Yagasaki, F AU - Yagasaki F FAU - Yakata, Y AU - Yakata Y FAU - Matsuo, T AU - Matsuo T FAU - Kuriyama, K AU - Kuriyama K FAU - Tomonaga, M AU - Tomonaga M LA - eng PT - Journal Article PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Benzamides) RN - 0 (Piperazines) RN - 0 (Pyrimidines) RN - 8A1O1M485B (Imatinib Mesylate) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-abl) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Animals MH - Benzamides MH - Cell Division/drug effects MH - Female MH - Genes, abl MH - Humans MH - Imatinib Mesylate MH - Male MH - Mice MH - Piperazines/*pharmacology MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/pathology MH - Proto-Oncogene Proteins c-abl/*antagonists & inhibitors MH - Pyrimidines/*pharmacology EDAT- 2001/05/23 10:00 MHDA- 2001/06/02 10:01 CRDT- 2001/05/23 10:00 PHST- 2001/05/23 10:00 [pubmed] PHST- 2001/06/02 10:01 [medline] PHST- 2001/05/23 10:00 [entrez] AID - 10.1038/sj.leu.2402068 [doi] PST - ppublish SO - Leukemia. 2001 Apr;15(4):590-4. doi: 10.1038/sj.leu.2402068.