Research Summary

Development of a hypothesis-based proteogenomic discovery approach for next-generation applications in acute lymphoblastic leukemia (ALL)

Hypothesis:

Alteration(s) in IKZF1 (a B-cell developmental gene, functions as transcription factor), alone or in combination with other gene mutations, induce downstream signaling pathways that promotes leukemic cell survival on chemotherapy and risk of relapse in ALL. Combination of sensitive genomic and proteomic analyses along with functional studies can identify molecular biomarker(s) and pathways that can be used to further risk-stratify ALL patients and identify alternate targets for therapy. 

Aim:

The overall aim of the project is to identify predictive and prognostic biomarker of ALL for better risk stratification and alternative cost-effective therapeutic approach.

ALL therapy is risk-stratified using a complex algorithm. As a result of high-cost of treatment, outcomes in India and other developing countries have stagnated over the last 3 decades. The national ICiCLe protocol, a TTCRC initiative, has created a modern-yet-simplified clinical management process for childhood ALL. This brings with it the opportunity to ask questions about the treatment response as-well-as develop new cost-effective tools for risk stratification and also investigate alternative therapeutic options in terms of repurposing drugs. This proteogenomic study both in cell lines as-well-as in patients with known IKZF1 status will have impact on alternative treatment strategy for ALL patients in India.

 

Figure Legend: Experimental Strategies for identification predictive and prognostic biomarkers in childhood ALL