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Stem cell gene therapy using the MFGS-gp91phoxretroviral vector was performed on a 27-year-old patient with X-linked chronic granulomatous disease (X-CGD) in 2014. The patient’s refractory infections were resolved, whereas the oxidase-positive neutrophils disappeared within 6 months. Thirty-two months after gene therapy, the patient developed myelodysplastic syndrome (MDS), and vector integration into the MECOMlocus was identified in blast cells. The vector integration into MECOMwas detectable in most myeloid cells at 12 months after gene therapy. However, the patient exhibited normal hematopoiesis until the onset of MDS, suggesting that MECOM transactivation contributed to clonal hematopoiesis, and the blast transformation likely arose after the acquisition of additional genetic lesions. In whole-genome sequencing, the biallelic loss of the WT1tumor suppressor gene, which occurred immediately before tumorigenesis, was identified as a potential candidate genetic alteration. The provirus CYBB cDNA in the blasts contained 108 G-to-A mutations exclusively in the coding strand, suggesting the occurrence of APOBEC3-mediated hypermutations during the transduction of CD34-positive cells. A hypermutation-mediated loss of oxidase activity may have facilitated the survival and proliferation of the clone with MECOM transactivation. Our data provide valuable insights into the complex mechanisms underlying the development of leukemia in X-CGD gene therapy.

An egg parasitoid, Trissolcus japonicus(Ashmead) (Hymenoptera: Scelionidae), was reared on eggs of Plautia staliscott (Hemiptera: Pentatomidae), Halyomorpha halys(Stål) (Hemiptera: Pentatomidae), and Glaucias subpunctatus(Walker) (Hemiptera: Pentatomidae), and parasitism rates and developmental properties were compared to clarify their suitability as hosts. The parasitoids successfully emerged from more than 90% of P. stalior G. subpunctatuseggs,whereas a lower rate of T. japonicusemerged from the eggs of H. halys.The developmental period of T. japonicusin the eggs of H. halyswas longer than in the other two species, and the body size of T. japonicusthat emerged from the eggs of H. halyswas also larger than from the other two species. From these results, factors related to parasitism and developmental properties were discussed.