Tcl1 as a model for lymphomagenesis

Yuri Pekarsky, Nicola Zanesi, Rami Aqeilan, Carlo M. Croce*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

TCL1 was originally discovered as an oncogene activated in mature T-cell leukemias and was later proven to cause this disorder. Several key studies in the last 3 years significantly expanded the importance of this gene to a wide spectrum of leukemias and lymphomas. It seems likely that for every hematopoietic cell type with low or absent Tcl1 expression, there is a leukemia involving the deregulation of TCL1. Although the general importance of TCL1 in mature T- and B-cell leukemias/lymphomas is clear, the detailed molecular mechanisms behind its oncogenic function have just begun to emerge. The discovery that Tcl1 is a coactivator of Akt shed some light on the function of this protein. The fact that Tcl1 translocates to the nucleus suggests a nuclear function for Akt and the existence of Akt targets in the nucleus. Because a comprehensive study of physical interactions of Tcl1 with other proteins is lacking, it is not clear whether involvement in Akt pathway is the only function of Tcl1 or other whether molecular mechanisms of Tcl1 exist. The next question is how to use the accumulated genetic and biochemical data of Tcl1/Akt oncogenic pathway for the diagnosis or treatment of leukemias of mature phenotype. Tcl1 does not have a known enzymatic activity and therefore cannot be inhibited. The inhibition of Akt may be too broad and unspecific to be used. It seems likely that the disruption of Tcl1-Akt interaction might be a promising but technologically challenging approach. Alternatively, we need to identify and use downstream targets (such as Nur77) of this oncogenic mechanism. Further understanding of Tcl1 signaling is required to develop specific therapies for leukemias/lymphomas caused by TCL1 deregulation.

Original languageAmerican English
Pages (from-to)863-879
Number of pages17
JournalHematology/Oncology Clinics of North America
Volume18
Issue number4
DOIs
StatePublished - Aug 2004
Externally publishedYes

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