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T cell acute lymphoblastic leukemia downstream regulatory networks clarified

09-26-2006

Recent research from the United States has reported on the clarification of transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia (T-ALL).

"Aberrant expression of 1 or more transcription factor oncogenes is a critical component of the molecular pathogenesis of human T-ALL; however, oncogenic transcriptional programs downstream of T-ALL oncogenes are mostly unknown," wrote T. Palomero and colleagues, Columbia University.

"TAL1/SCL is a basic helix-loop-helix (bHLH) transcription factor oncogene aberrantly expressed in 60% of human T-ALLs. We used chromatin immunoprecipitation (ChIP) on chip to identify 71 direct transcriptional targets of TAL1/SCL.

"Promoters occupied by TAL1 were also frequently bound by the class I bHLH proteins E2A and HEB, suggesting that TAL1/E2A as well as TAL1/HEB heterodimers play a role in transformation of T-cell precursors. Using RNA interference, we demonstrated that TAL1 is required for the maintenance of the leukemic phenotype in Jurkat cells and showed that TAL1 binding can be associated with either repression or activation of genes whose promoters occupied by TAL1, E2A, and HEB," reported the authors.

"In addition, oligonucleotide microarray analysis of RNA from 47 primary T-ALL samples showed specific expression signatures involving TAL1 targets in TAL1-expressing compared with -nonexpressing human T-ALLs," the scientists added.

They concluded, "Our results indicate that TAL1 may act as a bifunctional transcriptional regulator (activator and repressor) at the top of complex regulatory network that disrupts normal T-cell homeostasis and contributes to leukemogenesis."

Palomero and colleagues published their study in Blood (Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia. Blood, 2006;108(3):986-992).

For additional information, contact A.A. Ferrando, Columbia University, Institute of Cancer Genetics, 1150 St. Nicholas Avenue, Rm 318A, New York City, NY 10032, USA.

Publisher contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA.

Keywords: New York, New York, United States, Immunology, Leukemia, Oligonucleotide Microarrays, T Cells, Transcriptional Regulation.

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