CoChat
Sign Up
Cited by 482

The DOI matches its Crossref record.

The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells

Deininger, Michael W.N., Goldman, John M., Lydon, Nicholas, Melo, Junia V.·1997·Blood
DOI 10.1182/blood.v90.9.3691
Open this paper in CoChat — free account

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.

Overview

Integrity signals

Registry

Crossref · 10.1182/blood.v90.9.3691

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 32

  1. Cortes, 1995, Philadelphia chromosome–negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long-term follow-up results., Cancer, 75, 464, 10.1002/1097-0142(19950115)75:2<464::AID-CNCR2820750209>3.0.CO;2-E · DOI
  2. Clark, 1988, Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL)., Science, 239, 775, 10.1126/science.3422516 · DOI
  3. Melo, 1996, The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype., Blood, 88, 2375, 10.1182/blood.V88.7.2375.bloodjournal8872375 · DOI
  4. Pane, 1996, Neutrophilic-chronic myeloid leukemia: A distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction)., Blood, 88, 2410, 10.1182/blood.V88.7.2410.bloodjournal8872410 · DOI
  5. Konopka, 1984, An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity., Cell, 37, 1035, 10.1016/0092-8674(84)90438-0 · DOI
  6. Spencer, 1995, Options for therapy in chronic myeloid leukaemia., Br J Haematol, 91, 2, 10.1111/j.1365-2141.1995.tb05236.x · DOI
  7. Italian, 1994, Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia., N Engl J Med, 330, 820, 10.1056/NEJM199403243301204 · DOI
  8. Hehlmann, 1994, Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group., Blood, 84, 4064, 10.1182/blood.V84.12.4064.bloodjournal84124064 · DOI
  9. Lugo, 1990, Tyrosine kinase activity and transformation potency of bcr-abl oncogene products., Science, 247, 1079, 10.1126/science.2408149 · DOI
  10. Kaur, 1994, Tyrphostin induced growth inhibition: Correlation with effect on p210bcr-abl autokinase activity in K562 chronic myelogenous leukemia., Anticancer Drugs, 5, 213, 10.1097/00001813-199404000-00013 · DOI
  11. Anafi, 1993, Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate., Blood, 82, 3524, 10.1182/blood.V82.12.3524.3524 · DOI
  12. Okabe, 1992, Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein–associated cell proliferations: Abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth., Blood, 80, 1330, 10.1182/blood.V80.5.1330.1330 · DOI
  13. Druker, 1996, Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells., Nat Med, 2, 561, 10.1038/nm0596-561 · DOI · Paper page
  14. Meydan, 1996, Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor., Nature, 379, 645, 10.1038/379645a0 · DOI
  15. Levitzki, 1995, Tyrosine kinase inhibition: An approach to drug development., Science, 267, 1782, 10.1126/science.7892601 · DOI
  16. Buchdunger, 1996, Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative., Cancer Res, 56, 100
  17. Diamond, 1995, BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual granulocyte-macrophage colony-forming unit colonies derived from blood of patients with chronic myeloid leukemia., Blood, 85, 2171, 10.1182/blood.V85.8.2171.bloodjournal8582171 · DOI
  18. Cross, 1993, Minimal residual disease after allogeneic bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: Correlations with acute graft-versus-host disease and relapse., Br J Haematol, 84, 67, 10.1111/j.1365-2141.1993.tb03026.x · DOI
  19. Cross, 1994, Appropriate controls for reverse transcription polymerase chain reaction (RT-PCR)., Br J Haematol, 87, 218, 10.1111/j.1365-2141.1994.tb04899.x · DOI
  20. Ono, 1995, Effects of low oxygen tension and antioxidants on human erythropoiesis in vitro., Exp Hematol, 23, 1372
  21. Maeda, 1986, Enhanced colony formation of human hemopoietic stem cells in reduced oxygen tension., Exp Hematol, 14, 930
  22. Lumley, 1996, Colony counting is a major source of variation on CFU-GM results between centres., Br J Haematol, 93, 49
  23. Keating, 1994, Variable transcription of BCR-ABL by Ph+ cells arising from hematopoietic progenitors in chronic myeloid leukemia., Blood, 83, 1744, 10.1182/blood.V83.7.1744.1744 · DOI
  24. Petzer, 1996, Characterization of primitive subpopulation of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia., Blood, 88, 2162, 10.1182/blood.V88.6.2162.bloodjournal8862162 · DOI
  25. Melo, 1996, Reverse transcription/polymerase chain reaction (RT/PCR) amplification of very small numbers of transcripts: The risk in misinterpreting negative results., Leukemia, 10, 1217
  26. Thijsen, 1996, Molecular analysis of hematopoietic colonies derived from chronic myeloid leukemia patients: Interphase fluorescence in situ hybridization compared with RT-PCR., Leukemia, 11, 301, 10.1038/sj.leu.2400563 · DOI
  27. Melo, 1993, The ABL-BCR fusion gene is expressed in chronic myeloid leukemia., Blood, 81, 158, 10.1182/blood.V81.1.158.158 · DOI
  28. Sawyers, 1994, The nuclear tyrosine kinase c-Abl negatively regulates cell growth., Cell, 77, 121, 10.1016/0092-8674(94)90240-2 · DOI
  29. Bedi, 1995, BCR-ABL–mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: A mechanism of resistance to multiple anticancer agents., Blood, 86, 1148, 10.1182/blood.V86.3.1148.1148 · DOI
  30. Evans, 1993, Activation of the Abelson tyrosine kinase activity is associated with suppression of apoptosis in hemopoietic cells., Cancer Res, 53, 1735
  31. Friesen, 1996, Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells., Nat Med, 2, 574, 10.1038/nm0596-574 · DOI
  32. Kim, 1993, Prostaglandin A2 and delta 12-prostaglandin J2 induce apoptosis in L1210 cells., FEBS Lett, 321, 209, 10.1016/0014-5793(93)80110-G · DOI

Cited by

See all 482

Metadata

Authors
Deininger, M. W. N., Goldman, J. M., Lydon, N., & Melo, J. V.
Affiliations
From the Leukaemia Research Fund Centre for Adult Leukaemia, Department of Haematology, Royal Postgraduate Medical School, London, UK; and Novartis, Basel, Switzerland.
Venue
Blood
Publisher
American Society of Hematology
Published
1997-11-01
Volume
90
Issue
9
Pages
3691-3698
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood.v90.9.3691
Cited by
482
References
0
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. https://app.cochat.ai/papers/10.1182/blood.v90.9.3691
The paper
Deininger, M. W. N., Goldman, J. M., Lydon, N., & Melo, J. V. (1997). The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood. https://doi.org/10.1182/blood.v90.9.3691