Research / Clinical Summary

Mitchell Diccianni, PhD Assistant Research Scientist, Pediatrics Contact by Email

Tremendous success as been attained in the treatment of pediatric cancers in the last 3 decades. T cell acute lymphoblastic leukemia was a fatal disease just 30 years ago and today harbors a >75% survival rate. Improved success of will rely on the characterization of the molecular defects present in these malignancies, the understanding of their function, and their exploitation for therapeutic intervention. We are using modern techniques of molecular biology to characterize candidate genes, search for new ones, and devise novel therapeutic interventions. By understanding the molecular risk factors for outcome in leukemia, we hope to be able to devise a therapeutic approach that is tailored to the genetic profile of the patient. Ultimately, we would like to be able to exploit the presence of a molecular defect to selectively target the leukemia cells themselves. We have previously identified the p16 gene as a tumor suppressor gene frequently inactivated in leukemia (Omura-Minamiwawa et al., 2000). Subsequently, we have exploited this inactivation to therapeutically target leukemic cells (Omura-Minamiwawa et al., 2000B; Batova et al. 1996; Diccianni et al. 2004). We are in the process now of not only identifying genes that may be involved in disease pathogenesis, but those that may predict patient outcome.

Recently, a new class of regulatory molecules have been identified known as MicroRNAs (miRNAs or miRs) (Pasquinelli, 2002; Bartel, 2004). True to their name, the active miR gene is only a 19-22-nucleotide species that is processed from a 60- to 110- nucleotide pre-miRNA hairpin transcript thought to derive from a longer pre-miRNA product. Though the function of genes are still unknown, miRNA inactivation may result in the overexpression of oncogenes, while miRNA activation may lead to the downregulation of tumor suppressor genes and/or those involved in apoptosis, cell cycle, invasion or angiogenesis. Using microarray, we have identified a number of Mir genes that appear to be differentially expressed in T-ALL. We hypothesize that one or more miR genes may be involved in T-ALL pathogenesis, and their expression profiles may predict patient outcome.

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