# Identification of a Novel, Oncogenic and Targetable TPR::ABL2 Fusion Gene in T‐Cell Acute Lymphoblastic Leukaemia

## TL;DR

A new TPR::ABL2 fusion gene was found in a high-risk T-cell leukemia case and shown to be treatable with existing drugs.

## Contribution

Discovery of a novel TPR::ABL2 fusion gene in T-ALL and its targetability with tyrosine kinase inhibitors.

## Key findings

- TPR::ABL2 fusion promotes cytokine-independent growth in Ba/F3 cells, showing its oncogenic potential.
- TPR::ABL2 exhibits kinase activation and is sensitive to tyrosine kinase inhibitors in both patient and cell models.
- The study expands the known ABL2 fusion repertoire in ALL and suggests TKIs as a treatment option.

## Abstract

ABL2 rearrangements represent a subtype of acute lymphoblastic leukaemia (ALL) associated with poor prognosis and survival. This study reports a high‐risk T‐cell ALL (T‐ALL) case with a novel TPR::ABL2 gene fusion resulting from a chromosomal deletion. Overexpression of TPR::ABL2 in Ba/F3 cells promoted cytokine‐independent growth, demonstrating its oncogenic nature. Both primary patient and Ba/F3 cells carrying TPR::ABL2 exhibited kinase activation and sensitivity to tyrosine kinase inhibitors (TKIs). This study expands the repertoire of ABL2 fusions identified in ALL and supports the incorporation of TKIs into T‐ALL treatment regimens to improve outcomes for this subtype.