https://openworks.mdanderson.org/sumexp21/1245/thumbnail.jp

Hayes, Kala

Pemberton, Jordan Ezekiel

Yannan, Jia

English

OpenWorks @ MD Anderson

Background• AML has been shown to be highlydependent on the expression BCLprotein family• BCL-2 inhibition has been shown to bea potent modailty in AML treatment• Thrombocytopenia in myelodysplasmicsyndromes range from 40-65%• AML has a 30% 5-year prognosis• 753B is a novel PROTACbioengineered to degradate the BCLfamily, specifically BCL2 and BCLXL• Coinically, 753B should have agreater affinity for targeting AML cellsspecifcially over other normal celltypes, avoiding thrombocytopeniaResultsConclusionsReferenceshttps://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq4) Porta et al. Pain Digest Pain 1998;8:346-352https://scholar.google.com/scholar?q=aml+treatment+cytopenia+prevalence&hl=en&as_sdt=0&as_vis=1&oi=scholart#d=gs_qabs&u=%23p%3DakASwHcut_sJ753B Efficacy in Acute Myeloid LeukemiaJordan Pemberton1, Jia Yannan1Department of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAMethodsWe treated various AML cell linesin vitro to observe the effects ofintroduction to 753B. We used theBioRad Western Blot system toobserve the levels of proteinexpression degradation asdifferent concentrations(0,37nm,111nm,333nm,1mm) inrespective cell lineages. We thenultilized a CTG assay to observerates of apoptosis induction in celllines exposed to different drugs atidentical concentrations. We usedimagestudio and microsoft excelfor data analysis and visulaization.24hrControl 37nm 111nm 333nm 1000nmOur experiments indicate that BCLXL isconsitently degradated upon exposure to753B. BCL2 seems to show moderate levelsof degradation but tends to not be assignificant or consistnent as BCLXL.Theobserved BCL2 resistance may be explainedby current research, which suggeststhat certain cells lines which express highelevels of TP73 show BCL2 inhibitionresistance. 753B also induces apoptosis atrates greater than or compareable to currentdrugs. Due to the specificity of 753B to AMLcells, compareable apopotic induction mayprove advantegous clinically, as the drug mayavoid side efects, such as thrombocytopeniainduction.BCLXLBCL2BCLXLBCLXLBCLXLBCL2BCL2BCL2Aim 1: Prove that 753B is effective in BCL protein degradationAim 2: Indicate the efficacy of 753B in comparison to venetoclax, navitoclax, DT2216

753B Efficacy in Acute Myeloid Leukemia

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1245&context=sumexp21

753B Efficacy in Acute Myeloid Leukemia

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