Leukemia research towards novel treatments

We have been interrogating the mechanistic basis for leukemogenesis through the analyses of a key leukemia gene, RUNX1, aiming for the development of novel diagnostic and therapeutic methods (Figure 1). Treatment of RUNX leukemia has a dismal outcome and novel therapeutic approaches are needed. Our experimental platforms inlcude a mouse system (knockout or transgenic mice), and molecular and cellular analyses on clinical samples. Using such strategy, we have identified many diagnostic markers and treatment methods.

Identification of cis-regulatory elements associated with human diseases

Human genome consists of 1.5% of coding and 98.5% of non-coding regions. Approximately 40% of disease-related genetic changes are expected to be located within the non-coding region, particularly in cis-regulatory elements (enhancer, silencer, locus control region, and insulator) which govern expression of genes. Genetic alterations in non-coding (intronic and intergenic) regions in RUNX loci have also been suspected to be the underlying mechanism for multiple human diseases; however, cis-elements for Runx family genes remain largely unknown. Employing our own unique strategy as shown in Figure 2, we have identified multiple cis-regulatory elements. Single nucleotide polymorphisms (SNPs) within these elements would serve as predictive risk factors for human diseases, whereas pharmaceutical modulation of the elements would lead to novel therapeutic directions.

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