T-cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) is
a lymphoproliferative disease derived from immunocompetent post-thymic T cells.
Activation (initiation of expression) of the TCL1locus at
chromosome 14q32.1 appears to be the causal event in the pathogenesis
of these mature T-cell leukemias. This activation occurs as a result of
or inversions that cause rearrangement of the TCL1
(T-cell leukemia/lymphoma 1) locus with regulatory elements of T-cell receptor
genes. To describe the molecular events that take part in the leukemogenesis
of mature T-cell leukemias, we reviewed the literature and our own data on
the molecular basis of mature T-cell leukemia. This data search revealed that
4 genes have been identified at the TCL1 locus: TCL1, TCL1b, TNG1, and TNG2. The expression of these genes is substantially increased following
rearrangements involving 14q32.1. Functional analysis of the Tcl1 protein
revealed its involvement in an Akt (protein kinase B) prosurvival pathway
through its interaction with the Akt kinase, which promotes translocation
of Akt to the nucleus and increases Akt's enzymatic activity. The available
data provide important insights into the molecular mechanisms of T-cell leukemogenesis
that may lead to the development of new drugs for treatment of mature T-cell
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