Chronic myeloid leukaemia (CML)
Chronic myeloid leukaemia is a blood cancer driven by a single fused gene, BCR-ABL. Imatinib in 2001 turned it from a disease with a median survival of about five years into one most people live with, and many can now stop treatment altogether.
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.
State of the art today
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
About 1-2 cases per 100,000 per year; because patients now live near-normal lifespans, prevalence keeps rising (SEER).
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
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.
Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase.
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.
TKI plus acute-leukaemia-type induction (ponatinib or dasatinib with chemotherapy), then allogeneic HSCT.
Subtypes & biomarkers
top- Chronic phase (~95% at diagnosis)
- Accelerated phase
- Blast phase (myeloid or lymphoid)
- Atypical CML / BCR-ABL1-negative (separate MDS/MPN entity)
- 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)
Target prevalence in this cancer
- 1960Philadelphia chromosome
Nowell and Hungerford describe a minute chromosome in CML: the first consistent chromosomal abnormality in a human cancer.
- 1973t(9;22) translocation
Janet Rowley shows the Philadelphia chromosome is a reciprocal translocation.
- 1990BCR-ABL causes CML in mice
Daley, Van Etten and Baltimore demonstrate the fusion kinase is sufficient to cause a CML-like disease.
- 1998Imatinib enters the clinic
Druker's phase 1 trial of STI571: complete haematologic responses in nearly every chronic-phase patient.
- 2001Imatinib approved
FDA approval in under three months; IRIS (2003) confirms superiority over interferon-cytarabine.
- 2006Second-generation TKIs
Dasatinib (2006) and nilotinib (2007) approved for resistance; later first line (DASISION, ENESTnd).
- 2012Ponatinib covers T315I; bosutinib approved
- 2018Treatment-free remission validated
EURO-SKI: about half of patients stopping TKI stay in remission.
- 2021Asciminib: allosteric STAMP inhibitor approved
ASCEMBL vs bosutinib in third line.
- 2024Asciminib first line
ASC4FIRST: higher MMR at 48 weeks than investigator-selected TKI; FDA accelerated approval October 2024.
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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- GIMEMARome, ITvia Imatinib, Minimal / molecular residual disease (MRD)
- via this cancer, Imatinib
- Seoul St. Mary's HospitalSeoul, KRvia Imatinib, Nilotinib
- American Society of HematologyWashington, DC, USvia Minimal / molecular residual disease (MRD)
- via Minimal / molecular residual disease (MRD)
- via Minimal / molecular residual disease (MRD)
- Central Drugs Standard Control OrganizationNew Delhi, INvia Imatinib
- European Hematology AssociationThe Hague, NLvia Minimal / molecular residual disease (MRD)
- via this cancer
- via Allogeneic stem cell transplantation
- Hospital Universitario 12 de OctubreMadrid, ESvia Minimal / molecular residual disease (MRD)
- HOVONRotterdam, NLvia Minimal / molecular residual disease (MRD)
- via Minimal / molecular residual disease (MRD)
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Allogeneic stem cell transplantation
- via Minimal / molecular residual disease (MRD)
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia Allogeneic stem cell transplantation
- via Allogeneic stem cell transplantation
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Minimal / molecular residual disease (MRD)
- via Minimal / molecular residual disease (MRD)
- via Minimal / molecular residual disease (MRD)
- via this cancer
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Allogeneic stem cell transplantation
Questions to ask
topQuestions to ask your oncologist about Chronic myeloid leukaemia
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example BCR-ABL1 by RT-qPCR on the International Scale, ABL1 kinase-domain mutations, ELTS score at diagnosis, Additional cytogenetic abnormalities, Cardiovascular risk profile), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Chronic phase, Accelerated phase, Blast phase.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Chronic phase, first line
- For my situation (chronic phase, first line), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Imatinib, Dasatinib, Nilotinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Resistance or intolerance
- For my situation (resistance or intolerance), which of the standard options do you recommend and why?Why: Guideline options include: Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase.
- Am I a candidate for Ponatinib, Asciminib, Bosutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Sustained deep molecular response
- For my situation (sustained deep molecular response), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Blast phase
- For my situation (blast phase), which of the standard options do you recommend and why?Why: Guideline options include: TKI plus acute-leukaemia-type induction (ponatinib or dasatinib with chemotherapy), then allogeneic HSCT.
- Am I a candidate for Ponatinib, Dasatinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Asciminib, Allogeneic stem cell transplantation?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Blast-phase CML: median survival still under a year”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Predicting who can stop TKI safely; second TFR attempts”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
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3key papers
2IRIS made imatinib the first-line standard for CML worldwide and established the tyrosine kinase inhibitor as a chronic, life-long oral therapy. For most patients CML became a manageable condition with near-normal life expectancy. Later generations of TKIs (dasatinib, nilotinib, asciminib) produce faster, deeper responses but have not shown a survival advantage over imatinib.
Druker's 2001 imatinib paper turned the idea of hitting a cancer's specific molecular engine into a working medicine. For people with CML it began the shift from a fatal disease treated with interferon or transplant to one managed with a daily tablet. It also set expectations, later tempered, that every cancer might have its own imatinib.
Latest papers
topQuery for this cancer: (TITLE:"Chronic myeloid leukaemia" OR ABSTRACT:"Chronic myeloid leukaemia" OR TITLE:"CML" OR ABSTRACT:"CML") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Chronic myeloid leukaemia (CML), not a curated reading list.