Targeting Apoptosis in AML

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Presentation transcript:

Targeting Apoptosis in AML

The Pathogenesis of AML

Strategies to Combat AML

Mechanism of BCL-2 Inhibition in AML: “Apoptosis Hypothesis”

Cells Use the BCL-2 Family of Proteins to Decide Whether to Die or to Survive

Venetoclax Is a Potent, Selective Inhibitor of BCL-2

Mechanism of BCL-2 Inhibition in AML: “Leukemia Stem Cell Hypothesis”

In Vivo Evidence of Decreased OXPHOS and Leukemia Stem Cell Targeting

Mechanism of BCL-2 Inhibition in AML: “Leukemia Stem Cell Hypothesis”

Mechanism of BCL-2 Inhibition in AML: “Leukemia Stem Cell Hypothesis” (Cont.)

Venetoclax + HMAs in Elderly Patients With Untreated AML: Study Design

Response Rates With Venetoclax + Baseline Therapy

Response Rates With Venetoclax + Baseline Therapy: Subgroup Analysis

Response Duration With Venetoclax + Backbone Therapy

OS With Venetoclax + Backbone Therapy

Frequencies of Common Recurrent Gene Mutations in Adults With AML

IDH1/2 and FLT3 Mutations in AML

BCL-2 Inhibition in Combination With Other Agents

Venetoclax With LDAC in Treatment-Naive, Elderly Patients With AML Unfit for Intensive CT: Efficacy

Venetoclax With LDAC in Treatment-Naive, Elderly Patients With AML Unfit for Intensive CT: Efficacy (Cont.)

Novel Combinations in Progress or Development: Front-Line Setting

Novel Combinations in Progress or Development: Relapsed Setting

Clinical Outcomes From BCL-2 Inhibition

Clinical Applications of BCL-2 Inhibition

Conclusions

Abbreviations

Abbreviations (cont)