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OHSU # 2648 — Methods of treating venetoclax-resistant acute myeloid leukemia


Acute myeloid leukemia (AML) is difficult to treat due to the genetic heterogeneity of the disorder and accompanying drug resistance observed in many patients.  Oregon Health & Science University researchers have identified a new therapeutic approach to overcome venetoclax resistance and improve outcomes and prognoses for AML patients experiencing drug resistance.

Technology Overview

BCL2 is commonly expressed in hematologic malignancies and is targeted by the therapeutic venetoclax to induce cell death in multiple leukemia cell lines. However, venetoclax is only modestly effective as a monotherapy in patients with AML, potentially due to the high degree of genetic diversity driving this cancer. Oregon Health & Science University researchers have identified genetic profiles associated with venetoclax sensitivity and resistance in AML patients. For patients that typically show drug resistance to venetoclax alone, further investigation has identified patient populations that may respond to specific venetoclax combination therapies. This includes patients that may benefit from combinations of venetoclax with NTRK inhibitors, CDK4/6 inhibitors, tyrosine kinase inhibitors, MAPK inhibitors, p38 inhibitors, BET/BRD4 inhibitors, and/or PI3 kinase inhibitors.  This method could advance precision medicine for oncology patients and ultimately improve the efficacy of venetoclax treatments and AML patient outcomes.


Romine et al., “ Monocytic differentiation and AHR signaling as Primary Nodes of BET Inhibitor Response in Acute Myeloid Leukemia.” Blood Cancer Discov. 2 (2021). Link

Eide et al., “Simultaneous kinase inhibition with ibrutinib and BCL2 inhibition with venetoclax offers a therapeutic strategy for acute myeloid leukemia,” Leukemia 34 (2020). Link

Kurtz et al., “Dual inhibition of JAK1/2 kinases and BCL2: a promising therapeutic strategy for acute myeloid leukemia.” Leukemia  32 (2018). Link

Zhang et al., “Biomarkers Predicting Venetoclax Sensitivity and Strategies for Venetoclax Combination Treatment.” Blood 132.1 (2018). Link

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Filed United States
Filed United States
Published United States WO 2020/092615
Published United States US 2021/0353619 A1