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.
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.
Authors: Audrey N Jajosky; James E Coad; Jeffrey A Vos; Karen H Martin; Jamie R Senft; Sharon L Wenger; Laura F Gibson Journal: Stem Cells Transl Med Date: 2014-05-22 Impact factor: 6.940
Authors: Dina B AbuSamra; Fajr A Aleisa; Asma S Al-Amoodi; Heba M Jalal Ahmed; Chee Jia Chin; Ayman F Abuelela; Ptissam Bergam; Rachid Sougrat; Jasmeen S Merzaban Journal: Blood Adv Date: 2017-12-26
Authors: Anna Wojtuszkiewicz; Gerrit J Schuurhuis; Floortje L Kessler; Sander R Piersma; Jaco C Knol; Thang V Pham; Gerrit Jansen; René J P Musters; Johan van Meerloo; Yehuda G Assaraf; Gertjan J L Kaspers; Sonja Zweegman; Jacqueline Cloos; Connie R Jimenez Journal: Mol Cell Proteomics Date: 2016-01-22 Impact factor: 5.911