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Cancers 2010, 2(4), 1838-1860; doi:10.3390/cancers2041838

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

* , ,  and
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 / Revised: 3 November 2010 / Accepted: 4 November 2010 / Published: 5 November 2010
(This article belongs to the Special Issue Cancer Diagnosis and Targeted Therapy)
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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 NF-κB; signaling; T cell; leukemia; lymphoma; NOTCH1; microenvironment
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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