关键词：白血病;干细胞;老化(生理学);血液细胞,癌症;化疗;造血细胞
摘 要：How leukemia stem cells gained resistance to radiation and chemotheraphy is poorly defined, yet critically determines how leukemia cells tolerate conventional leukemia therapy. Normal hematopoietic stem cells and leukemia initiating cells are known to share many functional properties. Therefore, they are supposed to utilize many common mechanistic pathways for their survival and migration. Using genetically engineered mice we demonstrated the functional roles of P2Y14 in preserving regenerative capacity by constraining senescence induction and molecular events governing it. Since P2Y14 is highly expressed in differentiation-resistant leukemia cells, P2Y14 expression in leukemia cells may also function in modulating the resistance to conventional cancer treatment. We believe these data define for the first time in mammals the identity and impact of a receptor modulating stem/progenitor tolerance of stress. By providing a mechanistic insight for the roles of P2Y14 in the stress-induced injury, our preliminary results are expected to provide the foundation for an effective treatment to destroy therapy resistant leukemia cells. In addition, we identified a nucleotide sugar, UDP-Glc, as a novel mobilizer of long-term repopulating HSPCs. This finding may also have important clinical implications in designing new mobilization strategies to improve the efficiency and outcome of autologous and allogeneic peripheral blood stem cell (PBSC) transplantation.