{"entity":{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","aka":[],"tldr":"The fusion that defines chronic myeloid leukaemia and a quarter of adult acute lymphoblastic leukaemia; the first cancer driver ever switched off by a pill.","summary":"t(9;22) creates a constitutively active ABL1 kinase. Imatinib (2001) transformed CML; dasatinib, nilotinib, bosutinib, ponatinib (covers T315I), and the allosteric STAMP inhibitor asciminib followed. In Ph+ ALL (~25% of adult B-ALL, rising with age), TKI plus chemotherapy or, increasingly, TKI plus blinatumomab without chemotherapy (D-ALBA) achieves deep molecular remissions and is reducing the need for transplant.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Philadelphia_chromosome","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Philadelphia_chromosome"}],"tags":["driver","fusion","kinase"],"related":["bcr-abl1-transcript","bcr-abl1-t315i"],"cancers":["all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","ponatinib","dasatinib","asciminib","omacetaxine"],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","bcr-abl1-signalling","cml-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"BCR-ABL1","role":[],"sources":[],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"Tumour-specific alteration: 2 of 2 label readouts filed under it measure a sequence variant (BCR::ABL1 T315I, BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)) absent from normal cells. HPA BCR: RNA low tissue specificity; high antibody staining in 6 normal tissues; highest cancer staining colorectal cancer (6 of 12 high). HPA ABL1: RNA low tissue specificity; high antibody staining in 1 normal tissue; highest cancer staining carcinoid (1 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); approvals of single-target medicines aimed at it also list Sarcomas (soft tissue, bone, GIST), Skin cancer (all types), not counted; Open Targets associates it with 9 specific cancer types at or above 0.5 (chronic myeloid leukemia, acute lymphoblastic leukemia, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans, myelodysplastic/myeloproliferative disease, myelodysplastic syndrome and more); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"BCR::ABL1 T315I label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16d804b6-4957-43ee-b18c-3b36ec37c5ac","note":"T315I-positive"},{"label":"BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=211ef2da-2868-4a77-8055-1cb2cd78e24b","note":"Ph+ CML (BCR::ABL1 present)"},{"label":"Human Protein Atlas BCR tissue","url":"https://www.proteinatlas.org/ENSG00000186716-BCR/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas ABL1 tissue","url":"https://www.proteinatlas.org/ENSG00000097007-ABL1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000186716 associations","url":"https://platform.opentargets.org/target/ENSG00000186716/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000097007 associations","url":"https://platform.opentargets.org/target/ENSG00000097007/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"BCR-ABL is a constitutively active tyrosine kinase that switches on RAS, PI3K, and STAT5. Kinase-domain mutations (T315I gatekeeper) drive TKI resistance.","whereFound":["CML (~100%)","Adult B-ALL (~25%; >40% over age 60)","Paediatric B-ALL (~3%)"],"targetClass":"kinase","prevalence":[{"cancerId":"all-leukemia","pct":"~25 adults; ~3 children","measure":"t(9;22)"}]},"route":"/targets/bcr-abl/","neighbours":{"biomarker":[{"id":"bcr-abl1-t315i","kind":"biomarker","name":"BCR::ABL1 T315I","route":"/biomarkers/bcr-abl1-t315i/"},{"id":"bcr-abl1-transcript","kind":"biomarker","name":"BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)","route":"/biomarkers/bcr-abl1-transcript/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"},{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","route":"/cancers/cml-advanced-phase/"},{"id":"cml-chronic-phase","kind":"cancer","name":"Chronic myeloid leukaemia, chronic phase","route":"/cancers/cml-chronic-phase/"},{"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/"},{"id":"all-paediatric-ph-positive","kind":"cancer","name":"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)","route":"/cancers/all-paediatric-ph-positive/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"bosutinib","kind":"drug","name":"Bosutinib","route":"/drugs/bosutinib/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"flumatinib","kind":"drug","name":"Flumatinib","route":"/drugs/flumatinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"nilotinib","kind":"drug","name":"Nilotinib","route":"/drugs/nilotinib/"},{"id":"olverembatinib","kind":"drug","name":"Olverembatinib","route":"/drugs/olverembatinib/"},{"id":"omacetaxine","kind":"drug","name":"Omacetaxine mepesuccinate","route":"/drugs/omacetaxine/"},{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"}],"pathway":[{"id":"bcr-abl1-signalling","kind":"pathway","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/pathways/bcr-abl1-signalling/"},{"id":"cml-signalling","kind":"pathway","name":"Chronic myeloid leukaemia (KEGG map)","route":"/pathways/cml-signalling/"},{"id":"oncogene-activation-two-hit","kind":"pathway","name":"Drivers, passengers & the two-hit model","route":"/pathways/oncogene-activation-two-hit/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"term":[{"id":"aneuploidy-theory-of-cancer","kind":"term","name":"Aneuploidy and chromosomal instability as the cause of cancer","route":"/terms/aneuploidy-theory-of-cancer/"},{"id":"abl1-kinase-domain-mutations","kind":"term","name":"BCR::ABL1 kinase domain mutations (T315I and others)","route":"/terms/abl1-kinase-domain-mutations/"},{"id":"ph-positive-all","kind":"term","name":"Ph-positive ALL","route":"/terms/ph-positive-all/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"}],"trial":[{"id":"d-alba","kind":"trial","name":"D-ALBA (GIMEMA LAL2116)","route":"/trials/d-alba/"},{"id":"phallcon","kind":"trial","name":"PhALLCON","route":"/trials/phallcon/"}],"target":[{"id":"abl1","kind":"target","name":"ABL1","route":"/targets/abl1/"},{"id":"lyn","kind":"target","name":"LYN kinase","route":"/targets/lyn/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"person":[{"id":"brian-druker","kind":"person","name":"Brian Druker","route":"/people/brian-druker/"},{"id":"bud-romine","kind":"person","name":"Bud Romine","route":"/people/bud-romine/"},{"id":"charles-sawyers","kind":"person","name":"Charles L. Sawyers","route":"/people/charles-sawyers/"},{"id":"janet-rowley","kind":"person","name":"Janet Rowley","route":"/people/janet-rowley/"},{"id":"owen-witte","kind":"person","name":"Owen N. Witte","route":"/people/owen-witte/"}],"paper":[{"id":"paper-druker-imatinib-phase1-nejm-2001","kind":"paper","name":"First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia","route":"/key-papers/paper-druker-imatinib-phase1-nejm-2001/"},{"id":"paper-iris-imatinib-nejm-2003","kind":"paper","name":"IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia","route":"/key-papers/paper-iris-imatinib-nejm-2003/"}],"institution":[{"id":"fox-chase","kind":"institution","name":"Fox Chase Cancer Center","route":"/institutions/fox-chase/"},{"id":"ohsu-knight","kind":"institution","name":"OHSU Knight Cancer Institute","route":"/institutions/ohsu-knight/"},{"id":"uchicago-cancer","kind":"institution","name":"University of Chicago Medicine Comprehensive Cancer Center","route":"/institutions/uchicago-cancer/"}],"company":[{"id":"ascentage-pharma","kind":"company","name":"Ascentage Pharma","route":"/companies/ascentage-pharma/"}]}}