# The histone demethylase JMJD1C in human Acute Myeloid Leukemia

> **NIH NIH R37** · J. CRAIG VENTER INSTITUTE, INC. · 2024 · $463,125

## Abstract

PROJECT SUMMARY
Current therapy for acute myeloid leukemia (AML) is inadequate. Despite newly available therapeutics agents,
the overall survival rate for patients with the disease is still poor. It was previously shown that JMJD1C, a histone
demethylase of KDM3 (lysine demethylase 3) family, is required for AML leukemogenesis but largely dispensable
for steady state hematopoiesis and therefore, a potential therapeutic target in AML. In a recent study, loss of
JMJD1C in leukemia cells was shown to lead to elevated RAS signaling pathway and increased sensitivity to
inhibitors against the pathway. Furthermore, the presence of RAS activating mutations that are common in AML
confer resistance to JMJD1C loss. These data led to the hypothesis that targeting RAS pathway in combination
with JMJD1C would be more effective in eliminating leukemia cells harboring activating RAS mutations. This
hypothesis will be tested by the following plan: i) efficacy of combining JMJD1C modulation with RAS pathway
inhibitors in treating AML with RAS mutations will be tested in mouse as well as xenograft models of AML; ii)
molecular mechanism of resistance to JMJD1C loss in AML with RAS mutations, as well as the role of
biomolecule condensates, emerging key regulator of transcription and AML leukemogenesis, in mediating the
molecular function of JMJD1C in AML will be studied. Overall, the proposed project, once accomplished, will
provide rational for the design of novel combination therapy for AML with co-occurring activating RAS mutations.

## Key facts

- **NIH application ID:** 10733065
- **Project number:** 7R37CA229751-06
- **Recipient organization:** J. CRAIG VENTER INSTITUTE, INC.
- **Principal Investigator:** Nan Zhu
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $463,125
- **Award type:** 7
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10733065

## Citation

> US National Institutes of Health, RePORTER application 10733065, The histone demethylase JMJD1C in human Acute Myeloid Leukemia (7R37CA229751-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10733065. Licensed CC0.

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