{"entity":{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","aka":[],"tldr":"Chronic myeloid leukaemia is a blood cancer driven by a single fused gene, BCR-ABL1, and the model for oncogene-targeted treatment: imatinib in 2001 and the tyrosine kinase inhibitors that followed turned it into a condition most people live with long-term. About half of patients with a sustained deep molecular response can now stop treatment altogether.","summary":"CML is defined by the Philadelphia chromosome t(9;22) and its product, the constitutively active BCR-ABL1 tyrosine kinase. It is the paradigm of oncogene addiction: tyrosine kinase inhibitors (TKIs) restore near-normal life expectancy in chronic phase, and treatment response is tracked by quantitative BCR-ABL1 PCR on the International Scale (IS), with milestones at 3, 6 and 12 months (ELN 2020).\n\nFirst-line options are imatinib, the second-generation TKIs dasatinib, nilotinib and bosutinib, and since 2024 asciminib (ASC4FIRST), the first allosteric STAMP inhibitor. Second-generation drugs achieve deeper responses faster but have not improved overall survival over imatinib; choice is driven by comorbidity (cardiovascular risk with nilotinib and ponatinib, pleural effusions with dasatinib) and by the goal of treatment-free remission (TFR). Resistance is largely through ABL1 kinase-domain mutations; T315I is covered by ponatinib and asciminib. Allogeneic transplant is reserved for blast phase or multi-TKI failure.\n\nThe frontier is TFR (about half of patients with sustained deep molecular response can stop, EURO-SKI), safer T315I coverage, olverembatinib in Asia, and the small residue of accelerated/blast-phase disease, where outcomes remain poor.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia","links":[{"label":"ELN 2020 recommendations","url":"https://www.nature.com/articles/s41375-020-0776-2"},{"label":"NCI PDQ: CML","url":"https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq"},{"label":"SEER: CML","url":"https://seer.cancer.gov/statfacts/html/cmyl.html"}],"tags":["gap-fill","haematologic"],"related":["cll","cmml","aml"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","allogeneic-hsct","mrd-testing","cytogenetics-fish"],"targets":["bcr-abl"],"drugs":["imatinib","dasatinib","nilotinib","bosutinib","ponatinib","asciminib","busulfan","omacetaxine"],"companies":["novartis","bms","pfizer","takeda"],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","cml-signalling"],"terms":["oncogene-addiction","mrd","resistance"],"trials":["nct04971226","nct03459534","nct05456191","dasision"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia-research"],"dependsOn":[],"notes":[],"group":"haematologic","burden":"About 1-2 cases per 100,000 per year; because patients now live near-normal lifespans, prevalence keeps rising (SEER).","subtypes":["Chronic phase (~95% at diagnosis)","Accelerated phase","Blast phase (myeloid or lymphoid)","Atypical CML / BCR-ABL1-negative (separate MDS/MPN entity)"],"biomarkers":["BCR-ABL1 by RT-qPCR on the International Scale (MMR = ≤0.1%, MR4.5 = ≤0.0032%)","ABL1 kinase-domain mutations (T315I, F317L, E255K/V, Y253H)","ELTS score at diagnosis","Additional cytogenetic abnormalities","Cardiovascular risk profile (drug selection)"],"standardOfCare":[{"setting":"Chronic phase, first line","approach":"Imatinib 400 mg, or a second-generation TKI (dasatinib, nilotinib, bosutinib), or asciminib (ASC4FIRST, approved 2024). Choice by comorbidity and treatment goal; monitor BCR-ABL1 IS at 3, 6, 12 months against ELN milestones.","refs":["imatinib","dasatinib","nilotinib","bosutinib","asciminib"],"guideline":{"nccn":"Category 1 (imatinib, dasatinib, nilotinib, bosutinib, asciminib)","version":"NCCN Guidelines: CML; ELN 2020 recommendations","url":"https://www.nature.com/articles/s41375-020-0776-2"}},{"setting":"Resistance or intolerance","approach":"Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase.","refs":["ponatinib","asciminib","allogeneic-hsct","bosutinib"],"guideline":{"version":"ELN 2020","url":"https://www.nature.com/articles/s41375-020-0776-2"}},{"setting":"Sustained deep molecular response","approach":"Treatment-free remission attempt after ≥3-5 years of TKI and ≥2 years of MR4 or better, with monthly PCR for the first six months (EURO-SKI); restart on loss of MMR.","refs":["mrd"],"guideline":{"version":"ELN 2020; EURO-SKI (Lancet Oncol 2018)","url":"https://doi.org/10.1016/S1470-2045(18)30192-X"}},{"setting":"Blast phase","approach":"TKI plus acute-leukaemia-type induction (ponatinib or dasatinib with chemotherapy), then allogeneic HSCT.","refs":["ponatinib","dasatinib","allogeneic-hsct"]}],"stateOfArt":["Life expectancy in chronic phase on TKI is close to the general population; the goal has moved from survival to deep molecular response and treatment-free remission.","Asciminib is the first allosteric BCR-ABL1 inhibitor and, since ASC4FIRST (2024), a first-line option with better tolerability than second-generation TKIs.","Roughly half of eligible patients maintain remission off therapy; predictors are duration of deep response and prior interferon exposure.","Blast-phase CML remains the unsolved problem, and TKI cost is the barrier in low- and middle-income countries despite generic imatinib."],"history":[{"year":1960,"title":"Philadelphia chromosome","note":"Nowell and Hungerford describe a minute chromosome in CML: the first consistent chromosomal abnormality in a human cancer.","refs":[]},{"year":1973,"title":"t(9;22) translocation","note":"Janet Rowley shows the Philadelphia chromosome is a reciprocal translocation.","refs":[]},{"year":1990,"title":"BCR-ABL causes CML in mice","note":"Daley, Van Etten and Baltimore demonstrate the fusion kinase is sufficient to cause a CML-like disease.","refs":[]},{"year":1998,"title":"Imatinib enters the clinic","note":"Druker's phase 1 trial of STI571: complete haematologic responses in nearly every chronic-phase patient.","refs":["imatinib"]},{"year":2001,"title":"Imatinib approved","note":"FDA approval in under three months; IRIS (2003) confirms superiority over interferon-cytarabine.","refs":["imatinib"]},{"year":2006,"title":"Second-generation TKIs","note":"Dasatinib (2006) and nilotinib (2007) approved for resistance; later first line (DASISION, ENESTnd).","refs":["dasatinib","nilotinib"]},{"year":2012,"title":"Ponatinib covers T315I; bosutinib approved","refs":["ponatinib","bosutinib"]},{"year":2018,"title":"Treatment-free remission validated","note":"EURO-SKI: about half of patients stopping TKI stay in remission.","refs":["mrd"]},{"year":2021,"title":"Asciminib: allosteric STAMP inhibitor approved","note":"ASCEMBL vs bosutinib in third line.","refs":["asciminib"]},{"year":2024,"title":"Asciminib first line","note":"ASC4FIRST: higher MMR at 48 weeks than investigator-selected TKI; FDA accelerated approval October 2024.","refs":["asciminib"]}],"pipeline":["asciminib","allogeneic-hsct","radotinib"],"openProblems":["Blast-phase CML: median survival still under a year.","Predicting who can stop TKI safely; second TFR attempts.","Cardiovascular toxicity of nilotinib and ponatinib.","Access to any TKI and to PCR monitoring in LMICs."],"parent":"leukaemia"},"route":"/cancers/cml/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"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":"cmml","kind":"cancer","name":"Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms","route":"/cancers/cmml/"},{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"mrd-kinetics-models","kind":"technology","name":"Residual disease kinetics (BCR-ABL halving and ctDNA slopes)","route":"/technologies/mrd-kinetics-models/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"abcb1","kind":"target","name":"ABCB1","route":"/targets/abcb1/"},{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"},{"id":"blk","kind":"target","name":"BLK","route":"/targets/blk/"},{"id":"eef2","kind":"target","name":"Elongation factor 2 (EEF2)","route":"/targets/eef2/"},{"id":"fgr","kind":"target","name":"FGR","route":"/targets/fgr/"},{"id":"fyn","kind":"target","name":"FYN","route":"/targets/fyn/"},{"id":"gab2","kind":"target","name":"GAB2","route":"/targets/gab2/"},{"id":"grb2","kind":"target","name":"GRB2","route":"/targets/grb2/"},{"id":"hck","kind":"target","name":"HCK kinase","route":"/targets/hck/"},{"id":"ifnar2","kind":"target","name":"IFNAR2","route":"/targets/ifnar2/"},{"id":"ifnar1","kind":"target","name":"Interferon alpha receptor (IFNAR1)","route":"/targets/ifnar1/"},{"id":"lyn","kind":"target","name":"LYN kinase","route":"/targets/lyn/"},{"id":"src","kind":"target","name":"SRC family kinases","route":"/targets/src/"},{"id":"srms","kind":"target","name":"SRMS","route":"/targets/srms/"},{"id":"yes1","kind":"target","name":"YES1","route":"/targets/yes1/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"bosutinib","kind":"drug","name":"Bosutinib","route":"/drugs/bosutinib/"},{"id":"busulfan","kind":"drug","name":"Busulfan","route":"/drugs/busulfan/"},{"id":"cytarabine","kind":"drug","name":"Cytarabine","route":"/drugs/cytarabine/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"flumatinib","kind":"drug","name":"Flumatinib","route":"/drugs/flumatinib/"},{"id":"hydroxyurea","kind":"drug","name":"Hydroxyurea (hydroxycarbamide)","route":"/drugs/hydroxyurea/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"mitobronitol","kind":"drug","name":"Mitobronitol","route":"/drugs/mitobronitol/"},{"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":"pipobroman","kind":"drug","name":"Pipobroman","route":"/drugs/pipobroman/"},{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"},{"id":"radotinib","kind":"drug","name":"Radotinib","route":"/drugs/radotinib/"}],"company":[{"id":"ascentage-pharma","kind":"company","name":"Ascentage Pharma","route":"/companies/ascentage-pharma/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"il-yang-pharmaceutical","kind":"company","name":"Il-Yang Pharmaceutical","route":"/companies/il-yang-pharmaceutical/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"shenzhen-targetrx","kind":"company","name":"Shenzhen TargetRx","route":"/companies/shenzhen-targetrx/"},{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"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/"}],"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":"clonal-evolution-theory","kind":"term","name":"Clonal evolution and the ecological view of cancer","route":"/terms/clonal-evolution-theory/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"},{"id":"sokal-elts-scores","kind":"term","name":"Sokal and ELTS risk scores (chronic myeloid leukaemia)","route":"/terms/sokal-elts-scores/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"}],"trial":[{"id":"nct05589896","kind":"trial","name":"A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies","route":"/trials/nct05589896/"},{"id":"nct06163430","kind":"trial","name":"A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)","route":"/trials/nct06163430/"},{"id":"nct03459534","kind":"trial","name":"A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs","route":"/trials/nct03459534/"},{"id":"nct04971226","kind":"trial","name":"A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP","route":"/trials/nct04971226/"},{"id":"nct05456191","kind":"trial","name":"A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)","route":"/trials/nct05456191/"},{"id":"nct05384587","kind":"trial","name":"Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia","route":"/trials/nct05384587/"},{"id":"dasision","kind":"trial","name":"DASISION","route":"/trials/dasision/"},{"id":"nct00493181","kind":"trial","name":"Interleukin 11, Thrombocytopenia, Imatinib in Chronic Myelogenous Leukemia (CML) Patients","route":"/trials/nct00493181/"},{"id":"nct06514534","kind":"trial","name":"Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.","route":"/trials/nct06514534/"},{"id":"nct03722420","kind":"trial","name":"Randomized Evaluation of Radotinib Versus Imatinib in Phase III Study for Efficacy With Chinese Patients (RERISE China)","route":"/trials/nct03722420/"},{"id":"nct03934372","kind":"trial","name":"Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors","route":"/trials/nct03934372/"},{"id":"nct05433532","kind":"trial","name":"Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients","route":"/trials/nct05433532/"},{"id":"nct06423911","kind":"trial","name":"Study of Olverembatinib (HQP1351) in Patients With CML-CP","route":"/trials/nct06423911/"},{"id":"nct04925479","kind":"trial","name":"Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia","route":"/trials/nct04925479/"},{"id":"nct07354074","kind":"trial","name":"Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP","route":"/trials/nct07354074/"},{"id":"nct06453902","kind":"trial","name":"TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients","route":"/trials/nct06453902/"},{"id":"nct04233346","kind":"trial","name":"The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation","route":"/trials/nct04233346/"}],"journal":[{"id":"clinical-lymphoma-myeloma-and-leukemia","kind":"journal","name":"Clinical lymphoma, myeloma & leukemia","route":"/journals/clinical-lymphoma-myeloma-and-leukemia/"},{"id":"current-hematologic-malignancy-reports","kind":"journal","name":"Current hematologic malignancy reports","route":"/journals/current-hematologic-malignancy-reports/"},{"id":"leukemia-and-lymphoma","kind":"journal","name":"Leukemia & lymphoma","route":"/journals/leukemia-and-lymphoma/"},{"id":"leukemia-research","kind":"journal","name":"Leukemia research","route":"/journals/leukemia-research/"}],"person":[{"id":"adrian-ochsenbein","kind":"person","name":"Adrian Ochsenbein","route":"/people/adrian-ochsenbein/"},{"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":"janet-rowley","kind":"person","name":"Janet Rowley","route":"/people/janet-rowley/"},{"id":"timothy-hughes","kind":"person","name":"Timothy P. Hughes","route":"/people/timothy-hughes/"}],"collection":[{"id":"leukemia-lymphoma-society","kind":"collection","name":"Leukemia & Lymphoma Society (LLS)","route":"/collections/leukemia-lymphoma-society/"}],"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/"}],"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/"}]}}