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Updated: Jan 8, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Published on: January 7, 2019

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Targeting CaMKIIδ overcomes therapy resistance in acute myeloid leukemia by suppressing the STAT3/CDK6/BCL-2 survival

Zhaoxing Wu1,2, Shuwen Zheng1,2, Mengyuan Li1,2

  • 1Department of Hematology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, College of Medicine.

Journal of Leukocyte Biology
|December 24, 2025
PubMed

Insights

Calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ) is a novel target in acute myeloid leukemia (AML). Inhibiting CaMKIIδ induces apoptosis and overcomes resistance, offering a new therapeutic strategy for AML patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Relapse and therapy resistance are significant challenges in acute myeloid leukemia (AML) treatment.
  • Identifying novel therapeutic targets is crucial for improving patient outcomes in AML.

Purpose of the Study:

  • To identify novel vulnerabilities and therapeutic targets in acute myeloid leukemia (AML).
  • To investigate the role of calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ) in AML pathogenesis and its potential as a therapeutic target.

Main Methods:

  • Analysis of CaMKIIδ expression in primary and relapse/refractory AML patient samples versus healthy donors.
  • Investigating the mechanistic effects of CaMKIIδ inhibition on AML cell apoptosis, STAT3 phosphorylation, cell cycle progression (CDK6), and BCL-2-dependent survival.
  • Evaluating the efficacy of the CaMKIIδ inhibitor hesperadin in vitro and in AML xenograft mouse models.

Main Results:

  • CaMKIIδ is aberrantly overactivated in AML patient samples, correlating with tumor burden and poor survival.
  • CaMKIIδ inhibition triggers rapid apoptosis in AML bulk and stem/progenitor cells by modulating key survival and cell cycle pathways.
  • Pharmacological inhibition of CaMKIIδ with hesperadin demonstrates potent anti-leukemic activity in vitro and in vivo, leading to sustained disease regression.

Conclusions:

  • CaMKIIδ is a critical regulator of AML cell survival and apoptosis, representing a novel vulnerability in the disease.
  • Targeting CaMKIIδ offers a promising preclinical strategy to overcome therapy resistance and improve outcomes in acute myeloid leukemia.
Keywords:
CaMKIIδacute myeloid leukemiahesperadintargeted therapy

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