NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic functions in Leukemic and in Microenvironmental Cells

Rodrigues Dos Santos, Nuno; Ghezzo, Marinella N.; Da Silva, Ricardo C.; Fernandes, Mónica T.

http://hdl.handle.net/10400.1/18400

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Authors

Rodrigues Dos Santos, Nuno

Ghezzo, Marinella N.

Da Silva, Ricardo C.

Fernandes, Mónica T.

Abstract(s)

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.