Hematopoietic stem/progenitor cells are less prone to undergo apoptosis than lymphocytes despite similar DNA damage response

Abstract

Hematopoietic stem/progenitor CD34+ cells (HSPC) give rise to all types of blood cells and represent a key cellular target for origination of leukemia. Apoptosis and repair of DNA double strand breaks (DSB) are vital processes in leukemogenesis. High doses of ionizing radiation are the best known agent that induces leukemia, but less is known about the leukemogenic potential of low doses. While umbilical cord blood (UCB) serves as a valuable source of the HSPC for both research and clinics, the data on DNA damage response and apoptosis in UCB HSPC are very limited. We have studied apoptosis and DSB in the UCB-derived CD34+HSPC and CD34- lymphocytes at different time points post-irradiation with low and therapeutic doses of γ-rays. DSB were enumerated with γH2AX foci using imaging flow cytometry. Different stages of apoptosis were analyzed using Annexin/7-AAD assay and γH2AX pan-staining by flow cytometry and imaging flow cytometry, respectively. Our results have consistently shown significantly higher resistance of CD34+ stem/progenitor cells to endogenous and radiation induced apoptosis as compared to CD34- lymphocytes. At the same time, no statistically significant difference was found in DSB repair between HSPC and lymphocytes as enumerated by the γH2AX foci. To conclude, we show for the first time that hematopoietic stem/progenitor cells are less prone to undergo apoptosis than lymphocytes what may be accounted for higher expression of anti-apoptotic proteins in CD34+ cells but was unlikely dealt with DSB repair.