# Development of Novel Therapeutic Strategies in Human Leukemias

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2020 · $2,012,011

## Abstract

Overall Program Summary
The overall goal of this program is to improve outcomes in the treatment of human leukemias with more
effective and less toxic therapies. We have made significant progress during the previous funding period in
understanding the genetic basis of acute myeloid leukemia (AML), developing more effective treatments for
human leukemias, and validating predictors of therapeutic response. Pre-clinical and clinical studies from Drs.
Griffin and Stone, funded by this P01, contributed directly to the FDA-approval of midostaurin for FLT3-mutant
AML during the last funding period. Work from Dr. Letai, funded by this P01, contributed directly to FDA-
approval of venetoclax for AML during the last funding period, to the demonstration that apoptotic priming
predicts response to therapy in leukemia. Work from Dr. Ebert, funded by this P01, elucidated the mechanism
of action of lenalidomide and its analogs, leading to widespread drug development in academia and the private
sector focused on protein degradation. And work from Dr. Armstrong, funded by this P01, led to a clinical trial
of a DOT1L inhibitor with evidence of response in AML. In this renewal, we propose studies to continue this
record of therapeutic development for leukemia, leveraging a sample bank, a clinical and genetic database, a
xenograft bank, and a team of laboratory and clinical investigators with a long and successful track record of
collaborative research. Specifically, we will investigate apoptotic priming and prediction of response to
targeted AML therapies in Project 1 (Dr. Letai); the targeting of CBL-mediated signaling and ubiquitin ligase
activity in Project 2 (Dr. Ebert); the modulation of the SALL4B transcription factor in Project 3 (Drs. Tenen,
Chai, and Qi); and the biology and therapeutic targeting of zinc finger transcription factors in Project 4 (Drs.
Armstrong and Fischer). Projects 2, 3, and 4 all focus on the modulation of ubiquitin ligase activity to develop
candidate therapeutics (Projects 3 and 4) or understand leukemia biology (Project 2). The team will use a
common set of drugs, assays, and model systems. All projects will characterize mutations in primary samples
using the Rapid Heme Panel, will test molecules in vitro using dynamic BH3 profiling with Dr. Letai (Project 1),
and will use a common set of xenografts. All projects will interact with Drs. Stone and Deangelo, leading
leukemia clinical investigators, to move candidate therapeutics into high impact clinical trials with deep
correlative studies. In aggregate, these studies will provide insights into leukemia biology, develop highly novel
therapeutic strategies, and lead to the advancements in the treatment of AML.

## Key facts

- **NIH application ID:** 9854833
- **Project number:** 2P01CA066996-21
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Benjamin Levine Ebert
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,012,011
- **Award type:** 2
- **Project period:** 1997-04-25 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854833

## Citation

> US National Institutes of Health, RePORTER application 9854833, Development of Novel Therapeutic Strategies in Human Leukemias (2P01CA066996-21). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9854833. Licensed CC0.

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