Hydrogen peroxide (H₂O₂) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner

Over the last few years, studies have suggested that oxidative stress plays a role in the regulation of hematopoietic cell homeostasis. In particular, the effects of hydrogen peroxide (H₂O₂) range from hematopoietic cell proliferation to cell death, depending on its concentration in the intracellular milieu. In this work, we evaluated the effects of an oxidative environment on normal and leukemic hematopoietic cells by stimulating normal human (umbilical cord blood) and murine (bone marrow) hematopoietic cells, as well as human myeloid leukemic cells (HL-60 lineage), upon H₂O₂ stimulus. Total cell populations and primitive subsets were evaluated for each cell type. H₂O₂ stimulus induces HL-60 cell death, whereas the viability of human and murine normal cells was not affected. The effects of H₂O₂ stimulus on hematopoietic stem/progenitor cell subsets were examined and the normal primitive cells were found to be unaffected; however, the percentage of leukemic stem cells (LSC) increased in response to H₂O₂, while clonogenic ability of these cells to generate myeloid clones was inhibited. In addition, H₂O₂ stimulus caused a decrease in the levels of p-AKT in HL-60 cells, which most likely mediates the observed decrease of viability. In summary, we found that at low concentrations, H₂O₂ preferentially affects both the LSC subset and total HL-60 cells without damage normal cells.