Session: 615. Acute Myeloid Leukemia - Therapy, excluding Transplantation: Poster II
Method: Two independent sets of experiments were performed by two separate research groups. One group was blinded to mutant versus wild type IDH status. The other group was blinded to drug identity including solvent versus BPTES and to various BPTES concentrations. Primary AML cells from patients were cultured in RPMI-1640 medium with 20% fetal bovine serum, 20% 5637 cell-conditioned medium and 1% antibiotics with no drug, DMSO control (0.1% concentration) and 20 or 40 microM BPTES. Cells were counted manually on days 2, 4 and 6. Growth curves were generated for viable cells as assessed by trypan blue exclusion. Experiments were performed in triplicates.
Results: Growth curves of primary AML cells (with mutation status indicated) with no drug and with DMSO or BPTES (20 or 40 microM) are shown in Figure 1. Cells #2, #3, #5 and #10 carried IDH1 mutations. Cells #4 and #9 were wild type. On day 4, there was approximately a two-fold decrease in the growth of all IDH-mutant AML cells exposed to 20 microM BPTES compared to DMSO. No significant difference in activity was observed between 20 and 40 microM of BPTES. There was no difference in cell growth between exposure to no drug and to DMSO. The growth of wild type AML cells was not significantly affected by the glutaminase inhibitor. Results were consistent between the two research groups.
Conclusions: Although IDH mutations are frequently found in AML, a therapeutic strategy targeted at these mutations has not been reported. To the best of our knowledge, this is the first report of a targeted approach to the treatment of IDH-mutant AML. We found that inhibition of glutaminase by a small molecule, BPTES, preferentially slows the growth of primary AML cells with mutant IDH1 versus those AML cells with wild type IDH. Further investigation in xenograft models and pharmacologic studies are ongoing.
Disclosures: No relevant conflicts of interest to declare.
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