# Impact of the senescent bone marrow microenvironment in AML biology

> **NIH CA R00** · TEMPLE UNIV OF THE COMMONWEALTH · 2026 · $249,000

## Abstract

Project Summary
Acute myeloid leukemia (AML) is the most common diagnosed adult leukemia, the median age of patients with
AML is about 70 years. Although the prognosis for younger adults with AML has improved during the last four
decades, there has been little progress in the treatment of older adults. Currently, approximately 90% of adults
with AML over the age of 55 will die due to resistance to therapy, relapse, or complications from harsh treatments
such as chemotherapy. AML disease progression is heavily influenced by supportive cells in the tumor
microenvironment. Bone marrow mesenchymal stromal cells (BMSCs) are an instrumental extrinsic component
to normal hematopoiesis which are hijacked by leukemic cells in the process of leukemia development. Based
on AML being mainly a disease of older adults and evidence of an accelerated aging phenotype in the (BM)
microenvironment of AML, this proposal aims to investigate the role of aging and senescence in AML disease
progression and to ultimately identify therapeutic targets and eliminate the leukemia-supportive aging phenotype
in the BM. Although epigenetic aging and senescence are two distinct but parallel mechanisms of aging, they
have been shown to converge where certain triggers of senescence can affect epigenetic age. The molecular
basis for age-related alterations in AML-derived BMSCs are poorly described and if deciphered, could have
significant implication on both the prevention and treatment of elderly AML. Moreover, the correlation of
epigenetic age in cells of the AML tumor microenvironment with outcome has not been examined. Thus, the
specific aims of this proposal are to (1) examine epigenetic, transcriptional and phenotypic differences in BMSCs
derived from AML patients, compared to age matched control BSMCs, enabled by the use of methylation studies,
sequencing, mass cytometry and biochemical assays (2) determine the epigenetic age via methylation analysis
of different components of the tumor microen

## Key facts

- **NIH application ID:** 11264870
- **Project number:** 5R00CA246083-06
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Amina  Abdul-Aziz
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2024-02-01T00:00:00 → 2027-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11264870

## Citation

> US National Institutes of Health, RePORTER application 11264870, Impact of the senescent bone marrow microenvironment in AML biology (5R00CA246083-06). Retrieved via AI Analytics 2026-07-06 from https://api.ai-analytics.org/grant/nih/11264870. Licensed CC0.

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