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. Our results strongly suggest that P2Y14/UDP-Glc axis plays an important role in stress-induced senescence and motility of HSPCs. As the expression of P2Y14 is preferentially high in drug-resistant leukemia cells, we anticipate that P2Y14/UDP-Glc axis governs the resistance and motility also in leukemia stem/progenitor cells.