biostudies-literatureUnknown5(4)Rozenbaum MVarda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv University (Dotan Research Center in Hemato-Oncology, Tel Aviv University)Varda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv UniversityAction for A-T (Action for AT)Action for A-TSomatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia-telangiectasia (A-T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A-T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A-T (ATM-/-), heterozygote donors (ATM+/-), and healthy donors. ATM-/- T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM-/- CAR T-cells was observed. Retroviral transduction of the CAR in ATM-/- T cells resulBlood cancer discovery267-275https://www.ebi.ac.uk/biostudies/studies/S-EPMC11215369biostudies-literatureGenotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells.PMC11215369Zinger TRechavi GJacoby ESarouk ISaar EGFluss RMeir AElitzur SRozenbaum MMarcu-Malina VJacob-Hirsch JfalseGenotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells.Somatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia-telangiectasia (A-T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A-T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A-T (ATM-/-), heterozygote donors (ATM+/-), and healthy donors. ATM-/- T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM-/- CAR T-cells was observed. Retroviral transduction of the CAR in ATM-/- T cells resul2024-01-01T00:00:00Z2024 Jul2026-06-02T12:08:16.514Z2026-04-18T03:10:59.364ZS-EPMC112153693874750110.1158/2643-3230.bcd-23-026810.1158/2643-3230.BCD-23-0268