# Identifying the mechanisms of leukemia progression

> **NIH NIH R35** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $767,359

## Abstract

PROJECT SUMMARY
Since 2002 when my laboratory discovered GATA1 mutations in all cases acute megakaryocytic leukemia in
children with Down syndrome, I have been at the forefront of defining the specific genetic events that promote
leukemia. I have extensively studied the role of GATA1 in normal and malignant hematopoiesis and gained many
insights into the contributions of several chromosome 21 genes, including DYRK1A, ERG and CHAF1B, in
leukemia. My laboratory is also well established in the field of the myeloproliferative neoplasms (MPNs),
especially in the role of megakaryocytes in the pathogenesis of myelofibrosis and the development of new
therapies for this disease. In this R35 application, I propose to focus my laboratory over the next 7 years (and
beyond) on understanding the mechanisms of leukemia progression from clonal hematopoietic disorders.
Specifically, we will identify and compare the ways that pediatric and adult disorders progress to acute myeloid
leukemia. We will leverage large scale CRISPR/Cas9 screening, animal models and primary patient samples to
deeply characterize the mechanisms of transformation and focus on answering three questions: 1) What are the
similar and disparate events that promote malignant progression of pediatric versus adult blood disorders? 2)
How does dysregulation of pathways downstream of identified tumor suppressor genes promote malignant
progression? 3) Which investigational or approved therapies can prevent progression or treat the tumors? The
answers to these questions will increase our basic understanding of cancer, reveal new therapeutic targets and
possibly shed light on chemoprevention strategies.

## Key facts

- **NIH application ID:** 10920372
- **Project number:** 5R35CA253096-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** John D Crispino
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $767,359
- **Award type:** 5
- **Project period:** 2021-09-22 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920372

## Citation

> US National Institutes of Health, RePORTER application 10920372, Identifying the mechanisms of leukemia progression (5R35CA253096-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10920372. Licensed CC0.

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