# Biomarkers of dasatinib response and resistance in T-cell acute lymphoblastic leukemia

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2022 · $587,189

## Abstract

Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children, with T-cell ALL accounting for 15% of
cases. T-ALL in children is associated with aggressive clinical features and inferior treatment response to
combination chemotherapy, compared to B-cell ALL. Further intensification of cytotoxic drug-based therapy is
ineffective for relapsed T-ALL and novel agents are much needed for these patients. We recently discovered
that a significant proportion of pediatric T-ALL exhibits exceptional response to tyrosine kinase inhibitor dasatinib,
in an ABL-independent fashion. Our preliminary genomic analyses pointed to the activation of the preTCR-LCK
signaling pathway as a potential driver of this drug response phenotype. We have developed an innovative
systems biology approach that integrates transcriptional profile with functional ex vivo drug testing in order to
develop a clinically translatable biomarker for sensitivity and resistance to dasatinib in T-ALL. We hypothesize
that our systems biology approach can comprehensively identify molecular determinants of dasatinib response
in T-ALL, and that dasatinib-sensitive T-ALLs have distinct clinical and genomic features.
In this project, we propose to 1) develop a systems biology-based biomarker model of dasatinib sensitivity in T-
ALL; 2) systematically characterize genomics and clinical features associated with dasatinib sensitivity in T-ALL,
and 3) explore mechanism of dasatinib resistance in T-ALL and develop biomarker-driven combination therapy
to overcome drug resistance.
Successful completion of these studies is likely to substantially shift the paradigm of how pediatric T-ALL is
treated and significantly impact the next generation of clinical trials and improve cure rates for children with this
devastating illness.

## Key facts

- **NIH application ID:** 10438869
- **Project number:** 5R01CA264837-02
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** David T. Teachey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $587,189
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438869

## Citation

> US National Institutes of Health, RePORTER application 10438869, Biomarkers of dasatinib response and resistance in T-cell acute lymphoblastic leukemia (5R01CA264837-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10438869. Licensed CC0.

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