Heat Shock Protein 90 Inhibition in Kasumi‐1 Leukemic Stem Cells

Abstract

Heat Shock Protein 90 (HSP90) is a well‐conserved chaperone protein present in all human cell types. In cancers, HSP90 protein expression is often upregulated as a result of the cancer cell's elevated metabolic rate and accumulation of mutations resulting in protein‐folding defects. Inhibition of HSP90 can be a potent anticancer strategy, and drugs that target HSP90 are currently in clinical trials. Luminespib (AUY922) is an HSP90 inhibitor that is currently undergoing clinical trials. This drug is unique in that it is one of the only HSP90 inhibitors known to target both the alpha‐ and beta‐isoforms of the protein. Various dosages of AUY922 were administered to the Kasumi‐1 acute myeloid leukemia cell line to evaluate the potency of AUY922. A Western Blot analysis was performed in three biological replicates to measure expression levels of Heat Shock Protein 70 (HSP70), a molecular partner of HSP90, that is upregulated when HSP90 is inhibited. A three‐colored flow cytometry experiment was conducted with CD34, CD38 and Live/Dead label to determine the effects of increasing dosages of AUY922 on both the overall population and specifically the stem cell population, which is thought to drive relapse. We showed that HSP90 inhibition flushes the cancer stem cell population in a dose‐responsive manner. This work may be important in furthering the discussion of drug development that targets the cancer stem cell population to promote durable remission and to prevent relapse.Support or Funding InformationSupported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence and by NIH Grant R15 CA186017.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.