# Integration of gene expression patterns, fusions, mutations, cytogenetics and other clinical variables for subtyping leukemias and targeting therapies

> **NIH NIH R50** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $154,500

## Abstract

Project Summary/Abstract
The recent discovery of the Ph-like subtype of childhood acute leukemia (ALL) represents a major breakthrough
in the understanding and management of this disease. This subgroup accounts for approximately one quarter
of all childhood high-risk ALL patients and is responsible for more than half of their deaths. The characteristic
gene expression signature of the Ph-like patients allows them to be identified at diagnosis and facilitates an in
depth characterization of their acquired underlying molecular abnormalities, including: gene fusions involving
tyrosine kinase genes and their pathways, translocations and deletions of CRLF2, mutations of JAK kinases and
insertions/deletions of IL7R. While the discovery of these fusions is still ongoing, many of these kinase events
have been shown to be responsive to tyrosine kinase inhibitors (TKIs) and other targeted therapies, making their
identification clinically crucial.
The proposed work is both a continuation of the characterization of Ph-like cases and also the application of the
Ph-like gene expression assay in clinical trials to permit the evaluation and development of targeted drug
therapies for these patients. This involves the initial testing of a very large prospective cohort of diagnostic ALL
samples to determine if the Ph-like signature is present. Simultaneously with the identification of the Ph-like
signature, testing for the most common CRLF2 fusion is also performed as well as a determination of the
likelihood of other CRLF2 rearrangements. The remaining Ph-like cases (comprising only about 10-15% of the
initial cohort) will then be subjected to transcriptomic sequencing (RNA-Seq) for the rapid identification of
expressed fusions, mutations and related insertions/deletions. This phase of the work will expand the discovery
of new fusions and also permit the assignment of known fusions to targeted therapies. The combination of the
discovery and characterization of these acquired events with full gene expression information will also allow new
predictive models and assays to be developed.
Within the next several years the culmination of this work is to transform the Ph-like ALL patients from the worst
outcome group to the best. The precedent for this has been the advent of TKI therapy for BCR-ABL1 patients.
Over the past ten years these patients have evolved from the poorest prognosis group to among the best
outcomes, principally due to the administration of appropriate targeted drugs. The challenge in doing this with
Ph-like patients has been the enormous diversity of gene fusions (currently more than 100) and the difficulty in
diagnosing and characterizing them. The application of the gene expression assay and sequencing strategy
described in this proposal address both of those issues and also allow for the targetable fusions to immediately
become part of clinical trials.

## Key facts

- **NIH application ID:** 9996511
- **Project number:** 5R50CA211542-05
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Richard C Harvey
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $154,500
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996511

## Citation

> US National Institutes of Health, RePORTER application 9996511, Integration of gene expression patterns, fusions, mutations, cytogenetics and other clinical variables for subtyping leukemias and targeting therapies (5R50CA211542-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996511. Licensed CC0.

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