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Effect of a Selective Abl Tyrosine Kinase Inhibitor, STI571, on in Vitro Growth of BCR-ABL-positive Acute Lymphoblastic Leukemia Cells

Effect of a Selective Abl Tyrosine Kinase Inhibitor, STI571, on in Vitro Growth of BCR-ABL-positive Acute Lymphoblastic Leukemia Cells

Y Kawaguchi, I Jinnai, K Nagai, F Yagasaki, Y Yakata, T Matsuo, K Kuriyama, M Tomonaga

Leukemia. 2001 Apr;15(4):590-4.

PMID: 11368361

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP778270114-A	Bcr-abl Inhibitor - CAS 778270-11-4		778270-11-4	Price

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