Expression of Bcl-2-related genes in normal and AML progenitors: changes induced by chemotherapy and retinoic acid (original) (raw)

Gieseler Papers on Apoptosis Research

Leukemia volume 13, pages 1881–1892 (1999)Cite this article

Abstract

The expression of Bcl-2 family members was examined in normal and leukemic hematopoietic cells. Immature hematopoietic progenitor cells (CD34+/33−/13−) did not express Bcl-2 but Bcl-XL, the majority of CD34 cells expressed Bcl-2, Bcl-XL and BAD, and normal promyelocytes (CD34−/33+) lacked expression of both Bcl-2 and Bcl-XL, while leukemic CD34+progenitors and promyelocytes expressed these anti-apoptotic proteins. In AML, Bcl-2 expression was higher on CD34+ than on all AML cells, however, expression of Bcl-2 or Bcl-XL did not predict achievement of complete remission. Surprisingly, low Bcl-2 content was associated with poor survival in a group of patients with poor prognosis cytogenetics. The anti-apoptotic BAD protein was found to be expressed in AML, but was phosphorylated in 41/42 samples. Phosphorylation was found at both sites, Ser 112 and Ser 136. During induction chemotherapy, Bcl-2 levels of CD34 cells increased significantly. In the context of evidence for small numbers of leukemic CD34+ cells expressing very high levels of Bcl-2 prior to therapy, this finding is interpreted as a survival advantage of Bcl-2 overexpressing progenitors and rapid elimination of cells with low Bcl-2. Bcl-2 and Bcl-XL were both expressed in minimal residual disease cells. Downregulation of Bcl-2 mRNA and protein was observed by ATRA and the combination of Ara-C, followed by ATRA, resulted in markedly increased cytotoxicity in HL-60 cells, as compared to Ara-C alone or ATRA followed by Ara-C. Implications of these findings for the development of new therapeutic strategies for AML are discussed.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Department of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    M Andreeff, S Jiang, X Zhang, M Konopleva, VE Snell, Z Xie, MF Okcu, G Sanchez-Williams, SM Kornblau & S Zhao
  2. Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Z Estrov
  3. Department of Biomathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    J Dong
  4. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    EH Estey
  5. Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    RC Champlin
  6. Burnham Institute, La Jolla, California, USA
    JC Reed

Authors

  1. M Andreeff
    You can also search for this author inPubMed Google Scholar
  2. S Jiang
    You can also search for this author inPubMed Google Scholar
  3. X Zhang
    You can also search for this author inPubMed Google Scholar
  4. M Konopleva
    You can also search for this author inPubMed Google Scholar
  5. Z Estrov
    You can also search for this author inPubMed Google Scholar
  6. VE Snell
    You can also search for this author inPubMed Google Scholar
  7. Z Xie
    You can also search for this author inPubMed Google Scholar
  8. MF Okcu
    You can also search for this author inPubMed Google Scholar
  9. G Sanchez-Williams
    You can also search for this author inPubMed Google Scholar
  10. J Dong
    You can also search for this author inPubMed Google Scholar
  11. EH Estey
    You can also search for this author inPubMed Google Scholar
  12. RC Champlin
    You can also search for this author inPubMed Google Scholar
  13. SM Kornblau
    You can also search for this author inPubMed Google Scholar
  14. JC Reed
    You can also search for this author inPubMed Google Scholar
  15. S Zhao
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Andreeff, M., Jiang, S., Zhang, X. et al. Expression of Bcl-2-related genes in normal and AML progenitors: changes induced by chemotherapy and retinoic acid.Leukemia 13, 1881–1892 (1999). https://doi.org/10.1038/sj.leu.2401573

Download citation

Keywords

This article is cited by