Proliferation And Apoptosis Of Ph~+ALL Cell S SUP-B15 Treated With HSP90 Inhibitor BIIB021

Backgroud and ObjectiveLeukemia is a hematopoietic malignancy that originates from hematopoietic stem and progenitor cells.Proliferative and survival advantages of leukemia cells in the body without controlled proliferation and accumulation,gradually replaced the normal hematopoiesis,and invade other organs and systems,so that patients with anemia,bleeding,infection and signs of infiltration,and ultimately lead to death.According to the cell series affected by leukemia cells,acute lymphoblastic leukemia(ALL)and acute myeloid leukemia(AML)are classified.The incidence of acute lymphoblastic leukemia(ALL)in China is 6.9/10 thousand.The treatment of acute lymphoblastic leukemia in adults draws on the successful experience of childhood ALL.About 30%-40%of patients are expected to be cured.For Ph+/BCR-ABL fusion gene positive ALL,The long-term disease-free survival rate is 40%-50%.The overall survival rate of elderly ALL was less than 10%.In this study,to intestigate the role of Hsp90 in proliferation and apoptosis influence of Ph~+ALL cells SUP-B15 through detecting the Hsp90 inhibitors BIIB021on Ph~+ALL SUP-B15cells.MethodsThe SUP-B15 cells were collected and treated with the HSP90 inhibitor BIIB021.the WST-1 was used to detect the effect of BIIB021on cell proliferation inhibition rate,FCM was used to detect the apoptosis of cells,semi-quantitative PCR was used to detect the expression of BCR-ABL mRNA and Hsp90 mRNA.Results:1.After BIIB021 treated the SUP-B15 cells in different stage,the SUP-B15cells growth was obviously inhibited with effect present dosage dependent(48h)(r=0.963);2.After the SUP-B15 cells indifferent stage were treated with different concentrations of BIIB021,the SUP-B15 cells showed significant apoptosis,and with dosage dependent manner(P<0.05);3.Hsp90 mRNA expression decreased significantly after SUP-B15 cells were treated with different concentrations of BIIB021for 48h,BIIB021 down-regulated the Hsp90mRNA expression in dosage dependent manner.(P<0.05),The drug did not decrease the level of mRNA of BCR-ABL.ConclusionHsp90 inhibitor BIIB021 can inhibit the proliferation of SUP-B15 cells,induce the apoptosis of SUP-B15 cells,and reduce the expression of Hsp90 mRNA.This study result provides laboratory basis for the treatment of Ph~+ALL patients.