Enhanced Sensitivity Of Philadelphia Chromosome-positive Leukemia Cells To Imatinib By MeAIB

Objective: Glutamine metabolism plays an important role in the development of leukemia and drug tolerance.The previous research and relative literature showed that high expression of glutamine transporter SLC38A1 is one of the independent factors of poor prognosis in acute myeloid leukemia.This study intends to investigate the expression of SLC38A1 in Philadelphia chromosome-positive(Ph+)leukemia cells,and to clarify the effect of the small molecule inhibitor Me AIB targeting SLC38A1 on the proliferation and apoptosis of Ph+ leukemia cells and the sensitivity of imatinib.Methods: Data were obtained from public databases through bioinformatics methods to compare the expression of SLC38A1 in different leukemia cells;RT-q PCR experimental method was used to detect the expression of SLC38A1 in Ph+ leukemia cells.Use the CCK-8 method to draw the cell growth curve and observe the effect of Me AIB on the growth of K562(Ph+ human acute myeloid leukemia cell line),sup-b15(Ph+ human acute lymphoblastic leukemia cell line),and compare with non-Ph+ Human leukemia cell lines such as molm13,U937.The CCK8 method was used to study the growth and proliferation of Ph+ leukemia cells by Me AIB and imatinib.At the same time,flow cytometry was used to detect the induction of apoptosis of leukemia cells by combined medication.Results:(1)SLC38A1 is highly expressed in Ph+ leukemia cell lines K562 and sup-b15,and the difference is statistically significant.(2)Compared with Phleukemia cells,the small molecule inhibitor Me AIB targeting SLC38A1 significantly inhibited the growth of K562 and sup-b15 leukemia cell lines.(3)Compared with single drug treatment,Me AIB combined with imatinib significantly inhibited the proliferation of K562 and sup-b15 leukemia cells,and significantly induced its apoptosis(P <0.05).Conclusions: The glutamine transporter SLC38A1 is highly expressed in Ph+ acute leukemia cells;the small molecule inhibitor Me AIB targeting SLC38A1 can inhibit the proliferation of Ph+ leukemia cells,and the combination with imatinib can significantly increase the growth inhibition and apoptosis of Ph+ leukemia cells,which preliminarily suggests that SLC38A1 may be a potential target for inhibiting the growth of Ph + leukemia cells,and Me AIB may be used to improve the sensitivity of Ph+ acute leukemia to tyrosine kinase inhibitors.