Targeting myeloid leukemia stem cells derived from induced pluripotent stem cells (iPSCs) using high-throughput screening of FDA-approved drugs to overcome drug resistance
Implementing Organization
Christian Medical College
Principal Investigator
Dr. RV Shaji
Christian Medical College
CO-Principal Investigator
Dr. Poonkuzhali B Christian Medical College
Tamil Nadu, Vellore-632004
Tamil Nadu, Ida Scudder Road
Project Overview
Myeloid leukemia is a rare disease caused by leukemic stem cells (LSCs) resistant to standard chemotherapy. In AML, patients respond to chemotherapy but relapse due to chemoresistant clones, while in CML, patients relapse after tyrosine kinase inhibitor (TKI) therapy withdrawal. Understanding the molecular basis of disease relapse and tailoring strategies to eliminate LSCs is challenging. Patient-derived induced pluripotent stem cells (iPSCs) offer a platform to study the pathophysiology of hematological malignancies. A study generated patient-derived iPSCs from myeloid leukemia stem cells, which will be used for drug screening targeting LSCs. Preliminary data from transcriptomic profiling revealed several novel targets differentially expressed in CML LSCs and chemoresistant AML cell lines. A protocol for reprogramming CD34+ cells from healthy donors and CML patients will be used to identify effective compounds to modulate these targets.