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NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells
IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
* Author to whom correspondence should be addressed.
Received: 15 October 2010; in revised form: 3 November 2010 / Accepted: 4 November 2010 / Published: 5 November 2010
Abstract: 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.
Keywords: NF-κB; signaling; T cell; leukemia; lymphoma; NOTCH1; microenvironment
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dos Santos, N.R.; Ghezzo, M.N.; da Silva, R.C.; Fernandes, M.T. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells. Cancers 2010, 2, 1838-1860.
dos Santos NR, Ghezzo MN, da Silva RC, Fernandes MT. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells. Cancers. 2010; 2(4):1838-1860.
dos Santos, Nuno R.; Ghezzo, Marinella N.; da Silva, Ricardo C.; Fernandes, Mónica T. 2010. "NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells." Cancers 2, no. 4: 1838-1860.