Tal‐1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha.

MA Kelliher, DC Seldin, P Leder - The EMBO journal, 1996 - embopress.org
MA Kelliher, DC Seldin, P Leder
The EMBO journal, 1996embopress.org
Ectopic activation of the TAL‐1 gene in T lymphocytes occurs in the majority of cases of
human T cell acute lymphoblastic leukemia (T‐ALL), yet experiments to date have failed to
demonstrate a direct transforming capability for tal‐1. The tal‐1 gene product is a serine
phosphoprotein and basic helix‐loop‐helix (bHLH) transcription factor known to regulate
embryonic hematopoiesis. We have established a transgenic mouse model in which tal‐1
mis‐expression in the thymus results in the development of clonal T cell lymphoblastic …
Ectopic activation of the TAL‐1 gene in T lymphocytes occurs in the majority of cases of human T cell acute lymphoblastic leukemia (T‐ALL), yet experiments to date have failed to demonstrate a direct transforming capability for tal‐1. The tal‐1 gene product is a serine phosphoprotein and basic helix‐loop‐helix (bHLH) transcription factor known to regulate embryonic hematopoiesis. We have established a transgenic mouse model in which tal‐1 mis‐expression in the thymus results in the development of clonal T cell lymphoblastic leukemia/lymphoma. Thus, overexpression of tal‐1 alone can be transforming, verifying its pathogenic role in human T‐ALL. In addition, leukemogenesis is accelerated dramatically by transgenic co‐expression of tal‐1 and the catalytic subunit of casein kinase IIalpha (CKIIalpha), a serine/threonine protein kinase known to modulate the activity of other bHLH transcription factors. Although tal‐1 is a substrate for CKII, the synergy of the tal‐1 and CKIIalpha transgenes appears to be indirect, perhaps mediated through the E protein heterodimeric partners of tal‐1. These studies prove that dysregulated tal‐1 is oncogenic, providing a direct molecular explanation for the malignancies associated with TAL‐1 activation in human T‐ALL.
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