The anti-apoptotic genes Bcl-X(L) and Bcl-2 are over-expressed and contribute to chemoresistance of non-proliferating leukaemic CD34+ cells

Br J Haematol. 2002 Aug;118(2):521-34. doi: 10.1046/j.1365-2141.2002.03637.x.


In acute myeloid leukaemia (AML), cell kinetic quiescence has been postulated to contribute to drug resistance. As the anti-apoptotic genes Bcl-2 and Bcl-X(L) have been implicated in cell cycle regulation, we investigated the expression of these genes in non-proliferating (Q) and proliferating (P) AML and normal CD34+ progenitor cells. Using reverse transcription polymerase chain reaction, Bcl-X(L) and Bcl-2 were overexpressed in Q versus P AML cells, whereas no difference in Bcl-XS and Bax expression was found. Furthermore, the Bcl-X(L)/X(S) but not the Bcl-2/Bax ratio was higher in Q AML compared with normal CD34+ Q cells (P = 0.001). An inverse correlation between Bcl-2 expression of leukaemic Q cells and their ability to enter the cell cycle was found. Treatment with all-trans retinoic acid (ATRA) reduced Bcl-2 and Bcl-X(L) expression in the leukaemic Q cells, and enhanced their chemosensitivity to cytosine arabinoside (ara-C). These findings demonstrate overexpression of the anti-apoptotic proteins Bcl-X(L) and Bcl-2 in quiescent CD34+ AML cells and suggest their involvement in the chemoresistance. The observed inverse correlation between Bcl-2 and proliferation suggests a role for Bcl-2 in the cell cycle regulation of AML. These findings could be used in the development of therapies that selectively induce apoptosis in quiescent leukaemic progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / genetics
  • Bone Marrow Cells / pathology
  • Cell Division
  • Cytarabine / pharmacology
  • Down-Regulation
  • Flow Cytometry / methods
  • Genes, bcl-2*
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tretinoin / pharmacology
  • bcl-X Protein
  • beta 2-Microglobulin / metabolism
  • fas Receptor / metabolism


  • Antigens, CD34
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • BCL2L1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • beta 2-Microglobulin
  • fas Receptor
  • Cytarabine
  • Tretinoin