Ectopic overexpression of INPP4B confers resistance to ara-C and reduces OS in vivo. (A) Cohorts of 3 to 8 NSG mice were given 105 MV4;11 cells transduced with wild-type INPP4B, phosphatase inactive INPP4B C842A mutant, or vector control intravenously after irradiation. After confirmation of engraftment on day 14, mice were left untreated (– araC) or treated with ara-C at 75 mg/kg intraperitoneally for 5 days, after which leukemia infiltration in the BM was quantified by flow cytometric assessment of MV4;11 cells expressing the Zsgreen1 reporter protein as well as human CD45 staining of BM cells. (A) BM analysis revealed that MV4;11 cells expressing both INPP4B and INPP4B C842A were resistant to ara-C administration compared with vector control. ***P < .0001; ns, not significant. (B) For survival analysis, cohorts of 7 to 8 NSG mice were engrafted with MV4;11 cells transduced with wild-type INPP4B, phosphatase inactive INPP4B C842A mutant, or vector control and treated with ara-C at 50 mg/kg intraperitoneally for 5 days and monitored until ethical euthanasia according to signs of morbidity. Survival was plotted by using the Kaplan-Meier method. P < .0001 for comparisons between vector control ands wild-type INPP4B (as indicated) and INPP4B C842A (not shown).
