Differences between the CD34+ and CD34- blast compartments in apoptosis resistance in acute myeloid leukemia.
OBJECTIVE
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.


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.


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.
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Amber
A
van Stijn
Marjolein A
MA
van der Pol
Alice
A
Kok
Petra M
PM
Bontje
Guido M J M
GM
Roemen
Rob H J
RH
Beelen
Gert J
GJ
Ossenkoppele
Gerrit J
GJ
Schuurhuis
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism / Q000502:physiology; D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis* / Q000378:metabolism; D017209:Apoptosis; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D015703:Antigens, CD; D018952:Antigens, CD34; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein