SUMMARY Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named “spautin-1” for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs.

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Key Points• There is a need to identify the best HLA haplotypemismatched related donor.• Use of young, male, NIMAmismatched donors results in the best survival after HLA haplotype-mismatched related donor transplants. Older sister donors were inferior to father donors with regard to NRM (HR 5 1.87; 95% CI 5 1.10-3.20; P 5 .02) and survival (HR 5 1.59; 95% CI 5 1.05-2.40; P 5 .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotypemismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms. (Blood. 2014; 124(6):843-850)

Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P 5 .34), respectively; the overall survival rate was 79% and 82% (P 5 .36), respectively; cumulative incidences of relapse were 15% and 15% (P 5 .98); and those of the nonrelapse-mortality were 13% and 8% (P 5 .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediateor high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940. (Blood. 2015;125(25):3956-3962)