# Dissecting the Mechanism of Acute Myeloid Leukemia Induced Bone Marrow Failure to Identify Therapeutic Interventions

> **NIH NIH K08** · STANFORD UNIVERSITY · 2020 · $163,291

## Abstract

PROJECT SUMMARY / ABSTRACT
Human acute myeloid leukemia (AML) is an aggressive blood cancer with a high mortality rate and poor
survival outcomes. The majority of AML patients die from complications arising from bone marrow
failure which causes decreased production of blood forming cells. However, we lack fundamental
knowledge regarding the mechanism driving this phenomenon.
Building upon recent data which shows near complete depletion of hematopoietic stem and progenitors
during AML expansion in human AML xenografts which occurred even with low level of disease burden,
the proposed work will define whether AML cell expansion displaces normal stem and progenitors from
the bone marrow environment into peripheral circulation (Aim 1) whereby they become entrapped in the
splenic endothelial and perivascular niche. This project also aims to characterize the splenic endothelial
and perivascular niche which remains poorly defined with respect to its cellular taxonomy and ability to
provide critical niche factors (Aim 2). These studies will be complemented by investigating the unique
oxysterol, 27-hydroxycholesterol, produced by AML cells in the dysregulation of normal hematopoiesis
in a paracrine manner (Aim 3).
This work will be performed under the primary mentorship of Dr. Ravi Majeti, an expert in the genetic
characterization and therapeutic targeting of AML cells using primary human AML xenografts. My co-
mentors, Dr. Irving Weissman and Dr. Hiro Nakauchi, are both renowned for their knowledge and
expertise in the characterization of hematopoietic stem and progenitors cells in the bone marrow and
spleen. This work will be conducted at Stanford University School of Medicine, a world-class research
institution. The results of the proposed work have the potential to translate existing, non-toxic and FDA
approved drugs into early phase clinical trials in a disease population that is very difficult to treat. If
funded, this award will allow me to pursue a rigorous training plan in normal and malignant
hematopoiesis, enabling me to expand my research across disciplines, learn new techniques, and acquire
the knowledge and skills to establish an independent laboratory focused on the reversal of bone marrow
failure in AML.

## Key facts

- **NIH application ID:** 9953785
- **Project number:** 1K08CA248940-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** TIAN YI ZHANG
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,291
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953785

## Citation

> US National Institutes of Health, RePORTER application 9953785, Dissecting the Mechanism of Acute Myeloid Leukemia Induced Bone Marrow Failure to Identify Therapeutic Interventions (1K08CA248940-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953785. Licensed CC0.

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