Evaluating the impact of mutant alleles on venetoclax and cytarabine sensitivity in acute myeloid leukemia (AML) cell lines

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

Acute Myeloid Leukemia (AML) is a common form of blood cancer that has a poor prognosis in older adults due to limited low-toxicity treatment options [1]. AML is a heterogenous disease that can be driven by several types of somatic mutations. Two common drugs used in in the treatment of AML are venetoclax and cytarabine. While these drugs have been shown to cause apoptosis of AML cells [2,3], it is unknown whether different genetic subtypes of AML respond differently to venetoclax and cytarabine. I hypothesize that OCI-AML2 and OCI-AML3 will have a different sensitivity to venetoclax and cytarabine because of their different mutational makeups. After 3-day and 5-day treatments of cytarabine, we saw that as concentrations of drug treatment increased this lead to lower cell viability in both cell lines. However, after a 3-day and 5-day venetoclax treatment, OCI-AML2 was sensitive to venetoclax while OCI-AML3 showed to resistance to the treatment. A combined treatment of both drugs was tested on the cell lines to see if using both drugs in combination would further reduce AML cell viability. While a combined treatment of cytarabine and venetoclax showed additive effect for OCI-AML2, there was no significant additive effect in OCI-AML3. Together, these data suggest that different in genetic mutations in AML may affect sensitivity to drug treatments.

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