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Differences between the CD34+ and CD34- blast compartments in apoptosis resistance in acute myeloid leukemia
Amber van Stijn1, Marjolein A van der Pol, Alice Kok
1Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Background And Objectives:
Altered expression of members of the Bcl-2 family might account for the observed apoptosis resistance to chemotherapy in acute myeloid leukemia (AML). Given the poor prognosis associated with CD34+ expression in AML, we studied the role of spontaneous apoptosis and apoptosis regulatory proteins in sorted CD34+ and CD34- primary AML fractions.
Design And Methods:
The expression levels of apoptosis regulatory proteins and spontaneous apoptosis were measured in primary AML samples by Western blot analysis and flow cytometry. To determine the role of CD34+ cells in apoptosis resistance, spontaneous apoptosis in serum-free conditions and apoptosis regulatory protein levels were measured in CD34+ and CD34- sorted cells from CD34+ primary AML samples.
Results:
We show that CD34+ AML fractions are more resistant to apoptosis than are corresponding CD34- AML fractions, and that this is paralleled by higher Bcl-2, Bcl-xL, Mcl-1, Pgp and lower Bax expression levels. Interestingly, as the percentage of CD34 cells increased in the primary AML sample, so too did the apoptosis resistance in the corresponding CD34- fraction, which was reflected by an increasing anti-apoptosis protein profile.
Interpretation And Conclusions:
The data show that the CD34+ fraction is more resistant to apoptosis than is the corresponding CD34- fraction and secondly that the AML as a whole is more apoptosis resistant with increasing CD34 percentage.