Browsing by Author "Ghezzo, Marinella N."
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- Cdkn2a inactivation promotes malignant transformation of mouse immature thymocytes before the β-selection checkpointPublication . Catarino, Telmo A.; Pacheco-Leyva, Ivette; Kindi, Faiza Al; Ghezzo, Marinella N.; Fernandes, Mónica T.; Costa, Telma; Rodrigues Dos Santos, NunoCDKN2A 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
- NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic functions in Leukemic and in Microenvironmental CellsPublication . Rodrigues Dos Santos, Nuno; Ghezzo, Marinella N.; Da Silva, Ricardo C.; Fernandes, Mónica T.Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.