Leukemia inhibition of retinoic acid receptor signaling by Ski was evaluated in acute myeloid leukemia (AML)

08-17-2006

"AML is a heterogeneous disease with multiple different cytogenetic and molecular aberrations contributing to leukemic transformation. We compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML patients (9 with -7/del7q and 11 with normal karyotype) with 23 CD34+ preparations from healthy bone marrow donors," researchers in Germany reported.

"SKI, a nuclear oncogene, was highly up regulated. In a second set of 183 AML patients analyzed with real-time PCR, the highest expression level of SKI in AML with -7/del7q could be confirmed. As previously described, Ski associates with the retinoic acid receptor (RAR) complex and can repress transcription. We wanted to investigate the interference of Ski with RAR alpha signaling in AML. Ski was co-immunoprecipitated and colocalized with RAR alpha.

"We also found that overexpression of wild-type Ski inhibited the prodifferentiating effects of retinoic acid in U937 leukemia cells. Mutant Ski, lacking the N-CoR binding, was no more capable of repressing RAR alpha signaling. The inhibition by wild-type Ski could partially be reverted by the histone deacetylase blocking agent valproic acid," explained M. Ritter and colleagues, Philipps University.

The researchers concluded, "Ski seems to be involved in the blocking of differentiation in AML via inhibition of RARa signaling."

Ritter and colleagues published their study in Leukemia (Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia. Leukemia, 2006;20(3):437-443).

For additional information, contact A. Neubauer, Philipps University, Innere Med Klin, Baldinger Str, D-35043 Marburg, Germany.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.