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

• Published in: Haematologica (Roma) 2003-05, Vol.88 (5), p.497-508
• Main Authors: van Stijn, A, van der Pol, MA, Kok, A, Bontje, PM, Roemen, GM, Beelen, RH, Ossenkoppele, GJ, Schuurhuis, GJ
• Format: Article
• Language: English
• Subjects: Acute Disease; Antigens, CD - analysis; Antigens, CD34 - analysis; Antigens, CD34 - metabolism; Apoptosis; ATP Binding Cassette Transporter, Sub-Family B - metabolism; ATP Binding Cassette Transporter, Sub-Family B - physiology; bcl-2-Associated X Protein; bcl-X Protein; Biological and medical sciences; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Leukemia, Myeloid - classification; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Tumor Cells, Cultured
• ISSN: 0390-6078; 1592-8721

Department 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.