Chronic myeloid leukaemia

Chronic myeloid leukaemia is a malignant clonal proliferation of an abnormal haemopoietic stem cell. Over a period of many months the cell line expands, producing myeloid cell types. Normal haemopoiesis is gradually replaced. (1,2,3)

Chronic myeloid leukaemia accounts for 20% of all leukaemias. It occurs mainly in middle aged and elderly people and is characterised by marked leucocytosis, a left shifted myeloid series and in 95% of patients, the Philadelphia chromosome.

• characteristic genetic abnormality of CML, the Philadelphia (Ph) chromosome, results from a reciprocal translocation between the long arms of chromosomes 9 and 22
• molecular consequence of this translocation is the fusion of the ABL gene (encoding a nonreceptor tyrosine kinase) with the BCR gene generating a chimeric gene BCR-ABL, which in turn is translated to a fusion protein (Bcr-Abl), a constitutively activated tyrosine kinase, which is present in virtually all patients with CML

CML develops insidiously. Initial symptoms are often nonspecific and due to anaemia or hypermetabolism. Weakness, weight loss and fatigue are common. Massive splenomegaly is characteristic and may cause left hypochondrial pain.

Approximately 90% of people with CML present with an indolent chronic phase of CML, defined as blasts of less than 10% in the blood or bone marrow, absence of extramedullary evidence of leukemia, basophils of less than 20%, and platelet counts of 100 to 1000 × 109/L (3):

• most advanced stage is CML blastic phase (CML-BP), characterized by the World Health Organization as 20% or more blasts/immature cells and by the MD Anderson Cancer Center and European LeukemiaNet as 30% or more.
  • approximately 1% to 2% of patients with CML present with CML-BP

Allogeneic bone marrow transplantation, the only curative treatment for CML, is associated with substantial morbidity and mortality and is limited to patients for whom a suitable donor is available.

Since 2000, first-generation tyrosine kinase inhibitors (TKIs) such as imatinib, and second-generation TKIs, such as bosutinib, dasatinib, and nilotinib, have improved CML-related mortality from 10% to 20% per year to 1% to 2% per year, such that patients with CML have survival rates similar to those of a general age-matched population (3).

Note:

• some patients with features of CML will not present with Philadelphia chromosome or BCR-ABL rearrangement
  • are considered to represent a separate disease entity and are referred to as Philadelphia negative and BCR-ABL negative, or atypical CML (4)

References

1. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020 Apr;34(4):966-84.
2. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(Suppl 4):iv41-51.
3. Jabbour E, Kantarjian H. Chronic Myeloid Leukemia: A Review. JAMA. Published online March 17, 2025.
4. Smith G, Apperley J, Milojkovic D, et al. A British Society for Haematology guideline on the diagnosis and management of chronic myeloid leukaemia. Br J Haematol. 2020 Oct;191(2):17c