Chronic myeloid leukaemia (CML) is a clonal myeloproliferative neoplasm characterized by sustained proliferation of myeloid lineages in the bone marrow and peripheral blood. The hallmark of most cases is the BCR-ABL1 fusion gene produced by the Philadelphia chromosome (t(9;22)(q34;q11.2)). This fusion encodes a constitutively active tyrosine kinase that drives signaling through pathways such as RAS/MAPK, PI3K/AKT, and JAK/STAT, promoting uncontrolled cell growth, resistance to apoptosis, and altered adhesion within the marrow microenvironment. Clinically, CML typically progresses through three phases: chronic, accelerated, and blast crisis. The chronic phase may present with nonspecific symptoms (fatigue, weight loss, night sweats), incidental leukocytosis, and a markedly enlarged spleen due to extramedullary haematopoiesis.
Diagnosis is guided by a combination of clinical assessment, blood counts, and definitive molecular testing. Peripheral blood frequently shows elevated white blood cell count with a spectrum of myeloid maturation forms (left shift), basophilia, and often thrombocytosis. Bone marrow examination demonstrates hypercellularity with granulocytic hyperplasia. However, confirmation relies on demonstrating BCR-ABL1. Quantitative real-time PCR (qRT-PCR) is used to measure BCR-ABL1 transcript levels and to monitor treatment response. Conventional cytogenetics can identify the Philadelphia chromosome, while fluorescence in situ hybridization (FISH) may be used when needed. Current response criteria categorize outcomes by the depth and timing of molecular response (for example, major molecular response and deeper milestones), which correlate with long-term progression-free survival.
The cornerstone of CML management is tyrosine kinase inhibitor (TKI) therapy. TKIs such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib inhibit BCR-ABL1 kinase activity, leading to reduction of leukemic burden and achieving molecular responses. Treatment is continued long-term, with dose optimization based on efficacy and tolerability. Resistance and suboptimal response can arise through BCR-ABL1 kinase domain mutations, increased drug efflux, clonal evolution, or poor adherence. Monitoring typically involves serial qRT-PCR to detect loss of response early and to guide switching among TKIs or escalating to therapies for resistant disease. Adverse effects vary by agent and may include fluid retention and myelosuppression (more common with some TKIs), pleural effusion or pulmonary hypertension risk (certain agents), metabolic changes such as hyperglycaemia and dyslipidaemia (others), and thrombosis risk with more potent inhibitors.
When disease is resistant or when a deep, durable response cannot be achieved, allogeneic haematopoietic stem-cell transplantation (allo-HSCT) remains a potentially curative strategy. Allo-HSCT works by replacing the patient’s haematopoietic system with donor stem cells and leveraging a graft-versus-leukaemia effect mediated by donor immune cells. The procedure carries substantial risks, including graft-versus-host disease (GVHD), infections from profound immunosuppression, regimen-related toxicity, and transplant-related mortality. Therefore, patient selection is critical and generally considers age, comorbidities, disease phase, donor availability, prior TKI history, and the likelihood of obtaining an acceptable risk-benefit ratio. Reduced-intensity conditioning regimens have expanded eligibility for some older or medically frail patients while attempting to balance toxicity with disease control.
Supportive and survivorship care are integral. Patients may require management of anemia, bleeding risk, and infections, alongside vaccination planning and prophylactic antimicrobials when indicated. Cardiovascular risk assessment is important for several TKIs due to metabolic effects and vascular events. Psychosocial support is also vital: CML can impose chronic uncertainty due to lifelong therapy in many cases, and patients may experience anxiety related to relapse risk, treatment side effects, and frequent monitoring. Evidence-based coping strategies and clinician-led communication help improve adherence and quality of life.
Prognosis in CML has improved dramatically since the introduction of TKIs, with many patients achieving long-term survival and functional wellbeing. Outcomes depend on achieving early molecular milestones and maintaining response. For individuals who receive allo-HSCT, long-term outcomes can be favourable in appropriate candidates, particularly when transplantation occurs before advanced disease develops. Ongoing research focuses on optimizing treatment-free remission strategies in patients who achieve sustained deep molecular responses, refining mutation-informed TKI selection, and reducing transplant toxicity.
In summary, CML is driven by the BCR-ABL1 fusion kinase that sustains leukaemic proliferation through multiple downstream signaling cascades. Diagnosis hinges on molecular confirmation and quantitative monitoring, while treatment prioritizes TKI therapy and uses allo-HSCT for selected high-risk or resistant scenarios. Comprehensive monitoring and supportive care—medical and psychological—are central to durable outcomes. Source: CureLeukaemia (Fundraiser Friday post, Jun 5, 2026)
Cure Leukaemia: This Fundraiser Friday, we’re celebrating Mark! After being diagnosed with CML in 2017 and receiving a life-saving stem cell transplant, Mark has become an incredible supporter of Team CL. He’s completed our London 2 Paris ride multiple times and is even crewing the event right. #breaking
— @CureLeukaemia May 1, 2026
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