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

Catarino, Telmo A.; Pacheco-Leyva, Ivette; Kindi, Faiza Al; Ghezzo, Marinella N.; Fernandes, Mónica T.; Costa, Telma; Rodrigues Dos Santos, Nuno

http://hdl.handle.net/10400.1/20189

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Autores

Catarino, Telmo A.

Pacheco-Leyva, Ivette

Rodrigues Dos Santos, Nuno

Resumo(s)

CDKN2A deletion is the most frequent genetic alteration in T-cell acute lymphoblastic leukemia (T-ALL), occurring across all molecular and immunophenotypic subtypes. CDKN2A encodes two functionally unrelated tumor suppressor proteins, ARF and INK4a, which are critical regulators of cell cycle and proliferation. Arf has been reported to suppress T-ALL development in post−b-selection thymocytes, but whether CDKN2A acts as a tumor suppressor gene in immature, pre−b-selection thymocytes remains to be elucidated. Resorting to a Rag2-deficient model of T-ALL, driven by the ETV6:: JAK2 fusion, we report that Cdkn2a haploinsufficiency at early stages of T-cell development facilitates leukemia development