# Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukaemia

Source: https://onco.cc/key-papers/paper-roberts-ph-like-all-nejm-2014/  
OnCo record `paper-roberts-ph-like-all-nejm-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing showed that Ph-like acute lymphoblastic leukaemia, which behaves like Philadelphia-positive disease without the BCR-ABL1 fusion, is driven by a range of kinase-activating alterations, many of them potentially treatable with existing kinase inhibitors.

## Summary

Genomic study of 1,725 patients with B-ALL identifying the Ph-like subtype in 15 percent of children and over 25 percent of young adults, with transcriptome and genome sequencing of 154 Ph-like cases revealing ABL-class fusions, CRLF2 rearrangements with JAK mutations, and other JAK-STAT and Ras pathway lesions; cell lines and patient-derived xenografts responded to matching kinase inhibitors.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2014
- DOI: 10.1056/NEJMoa1403088
- Authors: Roberts KG, Li Y, Payne-Turner D, et al.
- Findings: Ph-like ALL frequency rises with age: about 10 percent of standard-risk children to over 25 percent of young adults.; Kinase-activating alterations in 91 percent of Ph-like cases; ABL-class fusions in about 13 percent.
- What it means: Screening for Ph-like ALL and its underlying kinase lesion is now part of high-risk ALL protocols, directing ABL-class cases to imatinib or dasatinib and JAK-pathway cases to ruxolitinib trials.
- Caveats: Efficacy of kinase inhibitors in Ph-like ALL is still being established in trials.

## Sources

- N Engl J Med 2014: https://doi.org/10.1056/NEJMoa1403088
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25207766/

## Connected records

- cancers: [Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)](https://onco.cc/cancers/all-ph-like/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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