# Dissecting the Roles and Requirements for RBM39 in Acute Myeloid Leukemia and Normal Hematopoiesis

> **NIH NIH K08** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $241,634

## Abstract

PROJECT SUMMARY/ABSTRACT
Research: RNA binding proteins (RBPs) regulate diverse cellular processes including transcription,
translation, and regulation of gene expression, and are frequently dysregulated in cancers. Through an
unbiased genetic screen aimed at identifying cancer-specific RBP dependencies, we recently identified
a specific requirement for RBM39 in malignant myeloid cancers and that cancers bearing RNA splicing
factor mutations as being particularly sensitive to the anti-cancer sulfonamides. RBM39 is an RBP that
functions in RNA splicing and recently, a class of clinical-grade “anti-cancer sulfonamide” compounds
were demonstrated to degrade RBM39 protein by co-opting the Ddb1/CUL4 ubiquitin-ligase complex as
their mechanism of action. Thus, the primary goal of this project is to assess differential and
tissue-specific requirements for RBM39 in normal hematopoiesis versus myeloid malignancies,
and to assess requirements for RBM39 for leukemia initiation and maintenance. This proposal will
utilize a novel conditional knockout (cKO) mouse for Rbm39 and several associated newly developed in
vitro and in vivo murine models to pursue this goal. We expect these investigations to further our
understanding of the role of RBM39 in normal physiology and cancer as well as provide new
therapeutic insights into the on- and off-target toxicities of the anti-cancer sulfonamides. These goals
are particularly timely given that several of these molecules have already proven excellent safety in
multiple phase I/II trials and are now ripe for therapeutic testing in a patient population most likely to
benefit from RBM39 degradation. Candidate: Dr. Sydney X. Lu is a graduating hematology & medical
oncology fellow in the Department of Medicine at MSKCC. He aims to become an independent, tenure-
track physician-scientist investigating the molecular pathogenesis of hematological malignancies through
a combination of genetics, functional genomics, and murine modeling. Dr.Lu has outlined a five-year period
of mentored training to strengthen his skills in functional genomics and disease modeling. This training
period will be carried out under the mentorship of Dr. Omar Abdel-Wahab, a leader in the functional
genomics of hematopoietic malignancies. Dr. Lu has also assembled an advisory committee composed of
Drs. Ross Levine, Martin Tallman, Michael Kharas, and Christine Mayr who will help guide his training
and research. Environment: MSKCC is the world's oldest and largest private cancer center, devoting
more than 130 years to exceptional patient care, innovative research, and outstanding educational
programs. MSKCC exposes trainees to an exceptionally robust academic research environment with a
strong commitment and track record of successfully supporting junior faculty who are seeking careers
as independent physician-scientists.

## Key facts

- **NIH application ID:** 9871252
- **Project number:** 1K08CA245242-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Sydney X Lu
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,634
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9871252

## Citation

> US National Institutes of Health, RePORTER application 9871252, Dissecting the Roles and Requirements for RBM39 in Acute Myeloid Leukemia and Normal Hematopoiesis (1K08CA245242-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9871252. Licensed CC0.

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