# Chronic myeloid leukaemia (CML)

Source: https://onco.cc/cancers/cml/  
OnCo record `cml` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

First-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.

The 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; haematologic
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/cml/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/cml/#overview [2 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/cml/#what-it-is [6 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/cml/#finding-it [5 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/cml/#treating-it [4 settings, 1 regimen, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/cml/#evidence [17 trials, 2 key papers, 10 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/cml/#science [18 targets, 5 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/cml/where-you-are/ [3 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/cml/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/cml/coming/ [16 medicines, 17 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/cml/data/ [101 connected records]

## Standard of care

- Chronic phase, first line: 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. ([Imatinib](https://onco.cc/drugs/imatinib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Asciminib](https://onco.cc/drugs/asciminib/))
- Resistance or intolerance: Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase. ([Ponatinib](https://onco.cc/drugs/ponatinib/), [Asciminib](https://onco.cc/drugs/asciminib/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Bosutinib](https://onco.cc/drugs/bosutinib/))
- Sustained deep molecular response: 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. ([Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/))
- Blast phase: TKI plus acute-leukaemia-type induction (ponatinib or dasatinib with chemotherapy), then allogeneic HSCT. ([Ponatinib](https://onco.cc/drugs/ponatinib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia
- ELN 2020 recommendations: https://www.nature.com/articles/s41375-020-0776-2
- NCI PDQ: CML: https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq
- SEER: CML: https://seer.cancer.gov/statfacts/html/cmyl.html

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/), [Chronic myeloid leukaemia, chronic phase](https://onco.cc/cancers/cml-chronic-phase/), [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Hairy cell leukaemia](https://onco.cc/cancers/hairy-cell-leukemia/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Residual disease kinetics (BCR-ABL halving and ctDNA slopes)](https://onco.cc/technologies/mrd-kinetics-models/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ABCB1](https://onco.cc/targets/abcb1/), [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [BLK](https://onco.cc/targets/blk/), [Elongation factor 2 (EEF2)](https://onco.cc/targets/eef2/), [FGR](https://onco.cc/targets/fgr/), [FYN](https://onco.cc/targets/fyn/), [GAB2](https://onco.cc/targets/gab2/), [GRB2](https://onco.cc/targets/grb2/), [HCK kinase](https://onco.cc/targets/hck/), [IFNAR2](https://onco.cc/targets/ifnar2/), [Interferon alpha receptor (IFNAR1)](https://onco.cc/targets/ifnar1/), [LYN kinase](https://onco.cc/targets/lyn/), [SRC family kinases](https://onco.cc/targets/src/), [SRMS](https://onco.cc/targets/srms/), [YES1](https://onco.cc/targets/yes1/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Busulfan](https://onco.cc/drugs/busulfan/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Flumatinib](https://onco.cc/drugs/flumatinib/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Imatinib](https://onco.cc/drugs/imatinib/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Mitobronitol](https://onco.cc/drugs/mitobronitol/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Olverembatinib](https://onco.cc/drugs/olverembatinib/), [Omacetaxine mepesuccinate](https://onco.cc/drugs/omacetaxine/), [Pipobroman](https://onco.cc/drugs/pipobroman/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Radotinib](https://onco.cc/drugs/radotinib/)
- companies: [Ascentage Pharma](https://onco.cc/companies/ascentage-pharma/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Il-Yang Pharmaceutical](https://onco.cc/companies/il-yang-pharmaceutical/), [Novartis](https://onco.cc/companies/novartis/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Shenzhen TargetRx](https://onco.cc/companies/shenzhen-targetrx/), [Takeda](https://onco.cc/companies/takeda/)
- pathways: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/), [Chronic myeloid leukaemia (KEGG map)](https://onco.cc/pathways/cml-signalling/), [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Aneuploidy and chromosomal instability as the cause of cancer](https://onco.cc/terms/aneuploidy-theory-of-cancer/), [BCR::ABL1 kinase domain mutations (T315I and others)](https://onco.cc/terms/abl1-kinase-domain-mutations/), [Clonal evolution and the ecological view of cancer](https://onco.cc/terms/clonal-evolution-theory/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/), [Sokal and ELTS risk scores (chronic myeloid leukaemia)](https://onco.cc/terms/sokal-elts-scores/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/)
- trials: [A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies](https://onco.cc/trials/nct05589896/), [A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)](https://onco.cc/trials/nct06163430/), [A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs](https://onco.cc/trials/nct03459534/), [A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP](https://onco.cc/trials/nct04971226/), [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)](https://onco.cc/trials/nct05456191/), [Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia](https://onco.cc/trials/nct05384587/), [DASISION](https://onco.cc/trials/dasision/), [Interleukin 11, Thrombocytopenia, Imatinib in Chronic Myelogenous Leukemia (CML) Patients](https://onco.cc/trials/nct00493181/), [Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.](https://onco.cc/trials/nct06514534/), [Randomized Evaluation of Radotinib Versus Imatinib in Phase III Study for Efficacy With Chinese Patients (RERISE China)](https://onco.cc/trials/nct03722420/), [Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors](https://onco.cc/trials/nct03934372/), [Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients](https://onco.cc/trials/nct05433532/), [Study of Olverembatinib (HQP1351) in Patients With CML-CP](https://onco.cc/trials/nct06423911/), [Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia](https://onco.cc/trials/nct04925479/), [Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP](https://onco.cc/trials/nct07354074/), [TGRX-678 Chinese Phase II in Chronic Myelogenous Leukemia (CML) Patients](https://onco.cc/trials/nct06453902/), [The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs or With T315I Mutation](https://onco.cc/trials/nct04233346/)
- journals: [Clinical lymphoma, myeloma & leukemia](https://onco.cc/journals/clinical-lymphoma-myeloma-and-leukemia/), [Current hematologic malignancy reports](https://onco.cc/journals/current-hematologic-malignancy-reports/), [Leukemia & lymphoma](https://onco.cc/journals/leukemia-and-lymphoma/), [Leukemia research](https://onco.cc/journals/leukemia-research/)
- people: [Adrian Ochsenbein](https://onco.cc/people/adrian-ochsenbein/), [Brian Druker](https://onco.cc/people/brian-druker/), [Bud Romine](https://onco.cc/people/bud-romine/), [Janet Rowley](https://onco.cc/people/janet-rowley/), [Timothy P. Hughes](https://onco.cc/people/timothy-hughes/)
- collections: [Leukemia & Lymphoma Society (LLS)](https://onco.cc/collections/leukemia-lymphoma-society/)
- key papers: [First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia](https://onco.cc/key-papers/paper-druker-imatinib-phase1-nejm-2001/), [IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia](https://onco.cc/key-papers/paper-iris-imatinib-nejm-2003/)
- institutions: [Fox Chase Cancer Center](https://onco.cc/institutions/fox-chase/), [OHSU Knight Cancer Institute](https://onco.cc/institutions/ohsu-knight/), [University of Chicago Medicine Comprehensive Cancer Center](https://onco.cc/institutions/uchicago-cancer/)
- biomarkers: [BCR::ABL1 T315I](https://onco.cc/biomarkers/bcr-abl1-t315i/), [BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)](https://onco.cc/biomarkers/bcr-abl1-transcript/)

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JSON: https://onco.cc/api/v1/entities/cml.json