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

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

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Received: 15 October 2010; in revised form: 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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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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.



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