# STUDIES OF BCR-ABL LEUKEMOGENESIS IN MICE

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $293,550

## Abstract

PROJECT SUMMARY/ABSTRACT
The Philadelphia chromosome–positive (Ph+) leukemias, including chronic myeloid leukemia (CML) and Ph+ B-
cell acute lymphoblastic leukemia (B-ALL), are prevalent blood cancers for which our current therapies are
inadequate. While BCR-ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have replaced
hematopoietic stem cell transplantation (HSCT) as initial therapy for CML, complete molecular remissions are
rare and acquired resistance to TKI therapy is a significant clinical problem. Eligible Ph+ B-ALL patients
undergo allogeneic HSCT in first remission following chemotherapy, but over half will relapse. Hence, it is likely
that current therapy will not cure most Ph+ leukemia patients, and effective methods to eradicate residual
leukemia are needed. To accomplish these goals, well-characterized mouse models of CML and B-ALL will be
utilized to investigate several highly relevant questions about the biology and pathogenesis of these leukemias
that are difficult to address using cell lines or primary human leukemia samples. In the first Aim, a binary
conditional transgenic mouse model of CML will be used to investigate the mechanism of primary resistance to
TKI therapy and determine if interventions that increase leukemia stem cell cycling increase the rate of
molecular remission. To extend adoptive cellular immunotherapy to myeloid leukemia, a chimeric antigen
receptor directed against a CML stem cell antigen will be developed and tested. In the second Aim, a novel
hypothesis that mutations in the transcription factor IKAROS underlie the biology of a major subset of high-risk
(Ph+ and Ph-like) B-ALL will be tested, and the mechanism of resistance of IKAROS-mutant B-ALL to therapy
determined. Together, these studies should yield important new knowledge that will improve the effectiveness
of our current treatments for Ph+ leukemia, and increase the proportion of patients that are cured of their
disease.

## Key facts

- **NIH application ID:** 10215400
- **Project number:** 5R01CA090576-21
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** RICHARD A. VAN ETTEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $293,550
- **Award type:** 5
- **Project period:** 2001-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215400

## Citation

> US National Institutes of Health, RePORTER application 10215400, STUDIES OF BCR-ABL LEUKEMOGENESIS IN MICE (5R01CA090576-21). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10215400. Licensed CC0.

---

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