# SPORE University of Texas M. D. Anderson Cancer Center-Leukemia

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $1,689,836

## Abstract

OVERALL PROJECT SUMMARY
Leukemias affect about 60,000 individuals, and cause the death of 24,000 individuals annually in the US. The
Leukemia SPORE renewal application builds upon progress achieved in the previous funding periods, which
contributed to several changes in the standards of care in leukemia. It proposes five important novel
mechanistic strategies which if successful, will establish new standards of therapies in leukemia: epigenetic
therapy modulation; immunotherapy with a new monoclonal antibody Hu-8F4; non-genotoxic p53 modulation
by MDM2 inhibition; novel natural-killer (NK) cellular therapy; targeting oxidative phosphorylation ( OxPhos) in
leukemia with novel OxPhos inhibitors. Our overall goal is to discover/enhance these new therapies through a
better understanding of the causal pathophysiologies in leukemia and the identification of actionable targets.
We propose five fully translational research projects (laboratory to clinic and back) supported by three cores.
The overall Specific Aims are: 1) Optimize and improve the efficacy of epigenetic therapies in AML
(Project 1). This research area was developed by Project 1 co-leaders over the past 14 years, and resulted in
the FDA approval of decitabine as an epigenetic therapy for MDS, and the European EMEA approval (2012)
for the treatment of elderly AML unfit for intensive chemotherapy. The new aims investigate enhancing the
epigenetic effects through suppression of CDK9. 2) Explore anti-leukemic effects of a novel targeted
immune therapy using 8F4 monoclonal antibody (Project 2). Previous work through this SPORE resulted
in the development of the PR1 vaccine and the discovery of a newly discovered humanized T cell receptor-like
antibody (8F4) with specificity for a conformational epitope of PR1 in vitro and in vivo. . Project investigators
will now test the efficacy of the new 8F4 antibody and conduct a phase I clinical trial to determine its anti- AML
efficacy, and understand the mechanisms behind its success/failure in patients treated. 3) Explore strategies
to enhance non-genotoxic p53 activation by MDM2 inhibition in AML (Project 3). Previous work
introduced p53-targeted therapy in leukemia as promising. Investigators will now extend these findings using
preclinical and clinical studies of novel MDM2 inhibitors and combinations with apoptosis inducing agents
(venetoclax). 4) Investigate NK-CAR cellular therapy in leukemia (Project 4). This is an in-house
therapeutic strategy funded through a Leukemia SPORE CEP and showing promising translational therapeutic
value. 5) Develop OxPhos- based targeted therapies in leukemia (Project 5). This is another in-house
developed approach and molecule investigated by investigators previously supported by a Leukemia SPORE
DRP, and expanded into a full project based on its promising results.

## Key facts

- **NIH application ID:** 10247497
- **Project number:** 5P50CA100632-19
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Marina Y Konopleva
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,689,836
- **Award type:** 5
- **Project period:** 2003-08-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247497

## Citation

> US National Institutes of Health, RePORTER application 10247497, SPORE University of Texas M. D. Anderson Cancer Center-Leukemia (5P50CA100632-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247497. Licensed CC0.

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