{"entity":{"id":"paper-roberts-ph-like-all-nejm-2014","kind":"paper","name":"Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukaemia","aka":[],"tldr":"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.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1403088"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25207766/"}],"tags":[],"related":[],"cancers":["all-ph-like"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1403088","pmid":"25207766","authors":"Roberts KG, Li Y, Payne-Turner D, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1725},"route":"/key-papers/paper-roberts-ph-like-all-nejm-2014/","neighbours":{"cancer":[{"id":"all-ph-like","kind":"cancer","name":"Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)","route":"/cancers/all-ph-like/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}