# Project 4: Role and Function of Sphingomyelin Synthase 1 in Leukemia

> **NIH NIH P01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $197,964

## Abstract

ABSTRACT
 The long-term goal of this project is to elucidate the role, regulation and therapeutic potential of
sphingomyelin synthase (SMS) in cancer. The current proposal focuses on the function of SMS1 in growth of
GATA1 positive leukemic cells (in particular, erythroblasts and megakaryoblasts) and on SMS1 as a potential
novel therapeutic target in acute myeloid leukemias (AML) that are enriched in such malignant immature
populations (particularly M6 and M7 AML).
 SMS represents a class of lipid-metabolizing enzymes that consumes ceramide and produces
diacylglycerol (DAG), two critical bioactive lipids with opposing functions in the control of key cellular processes
often dysregulated during transformation, including proliferation, apoptosis, and differentiation. Thus, SMS may
be linked to cancer, but knowledge on SMS regulation and downstream functions is limited.
 We previously showed that elevated expression of SMS1 is critical for proliferation of erythroleukemic
K562 cells. Published and preliminary results also show that the elevated expression of SMS1 is a
consequence of enhanced transcription occurring through a novel alternative promoter positively regulated by
the transcription factor GATA1. Guided by gene expression data from the Cancer Cell Line Encyclopedia, we
discovered that the highest SMS1 expression (mRNA and protein) in blood cancer cells is found in GATA1
positive AML blasts (erythroblasts and megakaryoblasts). Importantly, pharmacological and molecular
inhibition of SMS1 in these leukemic cells revealed a critical role for SMS1 in proliferation and survival of these
cells that is not observed in GATA1-negative AML blasts.
 Thus, based on these observations, we hypothesize that SMS1 is an important novel regulator of
proliferation and maintenance of GATA1 positive AMLs and a potential novel target for improving the
dismal therapeutic response of these leukemias. To address our hypothesis, we will: 1. Determine the role
and function of SMS1 in GATA1 positive AML cells and 2. Establish SMS1 as a novel target for
therapeutic intervention against GATA1 positive AMLs.
Our proposal aims at establishing SMS1 as a novel critical regulator of GATA1+ AML cells and might provide a
molecularly informed, and much needed novel therapeutic option for treatment of AML with erythroid or
megakaryocytic enrichment.

## Key facts

- **NIH application ID:** 10247637
- **Project number:** 5P01CA097132-18
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** CHIARA LUBERTO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,964
- **Award type:** 5
- **Project period:** 2003-08-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247637

## Citation

> US National Institutes of Health, RePORTER application 10247637, Project 4: Role and Function of Sphingomyelin Synthase 1 in Leukemia (5P01CA097132-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247637. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*