Tcl1 Regulated by miR-29, miR-181

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Cancer Res. 2006 Dec 15;66(24):11590-3.

Tcl1 Expression in Chronic Lymphocytic Leukemia Is Regulated by miR-

29 and miR-181.

Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov

V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps

T, Croce CM.

Comprehensive Cancer Center, Human Cancer Genetics Program and

Department of Molecular Virology, Immunology, and Medical Genetics,

OSU School of Medicine, Ohio State University, Columbus, Ohio.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common human

leukemia in the world. Deregulation of the TCL1 oncogene is a causal

event in the pathogenesis of the aggressive form of this disease as

was verified by using animal models.

To study the mechanism of Tcl1 regulation in CLL, we carried out

microRNA expression profiling of three types of CLL: indolent CLL,

aggressive CLL, and aggressive CLL showing 11q deletion. We

identified distinct microRNA signatures corresponding to each group

of CLL. We further determined that Tcl1 expression is regulated by

miR-29 and miR-181, two microRNAs differentially expressed in CLL.

Expression levels of miR-29 and miR-181 generally inversely

correlated with Tcl1 expression in the CLL samples we examined.

Our results suggest that Tcl1 expression in CLL is, at least in

part, regulated by miR-29 and miR-181 and that these microRNAs may

be candidates for therapeutic agents in CLLs overexpressing Tcl1.

(Cancer Res 2006; 66(24): 11590-3).