CD84 Levels Predict Venetoclax Response in Acute Myeloid Leukemia

Researchers report that CD84, a cell-surface molecule previously identified as a survival and redox regulator in acute myeloid leukemia (AML), appears to shape how leukemia cells respond to venetoclax, a drug now widely used in AML treatment regimens. According to the study, published in Experimental Hematology & Oncology, low CD84 expression was associated with favorable clinical response to venetoclax-based therapy, while high CD84 expression correlated with primary resistance. In paired samples taken at diagnosis and relapse, CD84 was up-regulated at relapse in two of three cases.

The team tested whether CD84 causally influences drug sensitivity rather than merely marking it. Genetic knockdown of CD84, as well as treatment with CD84-targeted CAR-T cells, sensitized AML cells to venetoclax in laboratory experiments and in cell-derived xenograft models in vivo. These findings suggest that CD84 is not only a predictive marker but also a potentially targetable vulnerability in resistant disease.

Mechanistically, the study points to SESN2, an antioxidant stress sensor, as a key downstream mediator. CD84 coordinates a pro-survival program that upregulates SESN2, which in turn suppresses mitochondrial reactive oxygen species and antagonizes the apoptosis triggered by venetoclax. Supporting this pathway, knockdown of SESN2 produced effects that phenocopied CD84 depletion, while overexpression of SESN2 partially restored venetoclax resistance in cells lacking CD84.

The authors conclude that CD84-mediated upregulation of SESN2 contributes to venetoclax resistance and may represent a potential therapeutic target to enhance treatment efficacy in AML. The evidence comes from preclinical models and a small set of paired patient samples, so the findings will require broader clinical validation before they can inform patient care.

Subject of Research: CD84 expression as a marker and driver of venetoclax resistance in acute myeloid leukemia

Article Title: CD84 expression stratifies venetoclax response and reveals a targetable vulnerability in resistant acute myeloid leukemia

Article References: Wang, X., Lin, X., Chen, T., Chen, Y., Wang, H., & Zhu, Y. (2026). CD84 expression stratifies venetoclax response and reveals a targetable vulnerability in resistant acute myeloid leukemia. Experimental Hematology & Oncology, 15(1), Article 90. https://doi.org/10.1186/s40164-026-00830-z

Image Credits: AI Generated

DOI: 10.1186/s40164-026-00830-z

Keywords: acute myeloid leukemia, venetoclax, CD84, SESN2, drug resistance, CAR-T cells, reactive oxygen species, apoptosis, hematology, biomarker, expression, stratifies