Technology Description

Researchers in Robi Mitra’s lab at Washington University in St. Louis have developed a method to increase the sensitivity of leukemias to chemotherapy by pre-treatment with a BET inhibitor. BET inhibitors convert stem-like leukemia cells to a more differentiated state that is more susceptible to standard chemotherapeutics like imatinib. As the persistence of these stem-like leukemia cells frequently drives chemotherapy resistance, pre-treatment with BET inhibitors would increase the efficacy of overall treatment.

Pre-treatment with JQ1 (BET inhibitor) decreases fraction of CD24^hi and increases efficacy of imatinib treatment

Stage of Research

The inventors showed that pre-treatment of leukemia cells in vitro with a BET inhibitor (JQ1) reduced the number of cells in a stem-like state (CD24^hi) and increased the potency of standard chemotherapeutic drugs like imatinib. They are following up on the initial proof-of-concept work with in vivo mouse studies.

Publications

• Moudgil A, Wilkinson MN, Chen X, He J, … & Mitra RD. (2020). Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells. Cell, 182:1-17.
• Cammack AJ, Moudgil A, Chen J, Vasek MJ, … & Dougherty JD. (2020). A viral toolkit for recording transcription factor-DNA interactions in live mouse tissue. PNAS, 117(18): 10004-10014.

Applications

• Treatment of leukemias in children and adults
• Potentially applicable to other cancers where the stem-like cell state is more resistant to chemotherapeutics

Key Advantages

• Increased efficacy of chemotherapies
• Utilizes existing drug classes

Patents: Pending

Related Web Links: Mitra Profile & Lab