Cdkn2a inactivation promotes malignant transformation of mouse immature thymocytes before the β-selection checkpoint

•Cdkn2a deletions occur in T-ALL driven by the ETV6::JAK2 fusion protein when the pre–TCR is absent.•Germline Cdkn2a inactivation favors malignant transformation of DN3 thymocytes.•Mouse T-ALL originating from Cdkn2a+/− DN3 thymocytes often presents Cdkn2a loss of heterozygosity.•Further secondary events occur in T-ALL originating from Cdkn2a+/− DN3 thymocytes.