DOI: 10.1182/blood.v90.9.3691. The Tyrosine Kinase Inhibitor CGP57148B Selectively Inhibits the Growth of BCR-ABL

The Tyrosine Kinase Inhibitor CGP57148B Selectively Inhibits the Growth of BCR-ABL–Positive Cells

10.1182/blood.v90.9.3691

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

Abstract The Philadelphia chromosome found in virtually all cases of chronic myeloid leukemia (CML) and in about one third of the cases of adult acute lymphoblastic leukemia is formed by a reciprocal translocation between chromosomes 9 and 22 that results in the fusion of BCR and ABL genetic sequences. This BCR-ABL hybrid gene codes for a fusion protein with deregulated tyrosine kinase activity that can apparently cause malignant transformation. CGP57148B, a 2-phenylaminopyrimidine derivative, has been shown to selectively inhibit the tyrosine kinase of ABL and BCR-ABL. We report here that this compound selectively suppresses the growth of colony-forming unit–granulocyte/macrophage (CFU-GM) and burst-forming unit–erythroid derived from CML over a 2-logarithmic dose range with a maximal differential effect at 1.0 μmol/L. However, almost all CML colonies that grow in the presence of 1.0 μmol/L CGP57148B are BCR-ABL–positive, which may reflect the fact that residual normal clonogenic myeloid precursors are infrequent in most patients with CML. We also studied the effects of CGP57148B on hematopoietic cell lines. Proliferation was suppressed in most of the BCR-ABL–positive lines; all five BCR-ABL–negative lines were unaffected. We conclude that this new agent may have significant therapeutic applications.

Bibliography

Deininger, M. W. N., Goldman, J. M., Lydon, N., & Melo, J. V. (1997). The Tyrosine Kinase Inhibitor CGP57148B Selectively Inhibits the Growth of BCR-ABLâPositive Cells. Blood, 90(9), 3691â3698.

Authors 4

Michael W.N. Deininger (first)
John M. Goldman (additional)
Nicholas Lydon (additional)
Junia V. Melo (additional)

References 32 Referenced 463

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Dates

Type	When
Created	5 years, 10 months ago (Oct. 12, 2019, 11:56 a.m.)
Deposited	5 years, 9 months ago (Nov. 19, 2019, 3:34 a.m.)
Indexed	1 month ago (July 31, 2025, 11:57 p.m.)
Issued	27 years, 10 months ago (Nov. 1, 1997)
Published	27 years, 10 months ago (Nov. 1, 1997)
Published Print	27 years, 10 months ago (Nov. 1, 1997)

Funders 0

None

BibTeX

@article{Deininger_1997, title={The Tyrosine Kinase Inhibitor CGP57148B Selectively Inhibits the Growth of BCR-ABL–Positive Cells}, volume={90}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v90.9.3691}, DOI={10.1182/blood.v90.9.3691}, number={9}, journal={Blood}, publisher={American Society of Hematology}, author={Deininger, Michael W.N. and Goldman, John M. and Lydon, Nicholas and Melo, Junia V.}, year={1997}, month=nov, pages={3691–3698} }

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