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STI571 Abl Tyrosine Kinase Inhibitor Studies

Effect of a selective Abl tyrosine kinase inhibitor, STI571, on in vitro growth of BCR-ABL-positive acute lymphoblastic leukemia cells

Leukemia volume 15, pages 590–594 (2001)Cite this article

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 140.3/104 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 μmol/l. None of the five BCR-ABL-negative ALL patients showed this growth inhibition by STI571 at 0.1–1.0 μmol/l. Our results indicate that STI571 selectively inhibits in vitro growth of BCR-ABL-positive ALL cells.

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Acknowledgements

We are grateful to Novartis Pharma, Inc. for providing STI571 and to Kirin Brewery Co. Ltd. for providing MS-5.

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Authors and Affiliations

  1. Department of Hematology, Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki, Japan

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

  2. First Department of Internal Medicine, Saitama Medical School, Saitama, Japan

    F Yagasaki

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  1. Y Kawaguchi
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Kawaguchi, Y., Jinnai, I., Nagai, K. et al. Effect of a selective Abl tyrosine kinase inhibitor, STI571, on in vitro growth of BCR-ABL-positive acute lymphoblastic leukemia cells. Leukemia 15, 590–594 (2001). https://doi.org/10.1038/sj.leu.2402068

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