Chronic myeloid leukemia (CML)

  • Myeloproliferative neoplasm (blood cancer)
  • New cases per year in Canada: 1-2 cases per 100 000 people per year (approx. 550 cases/year in Canada)
  • Median age at diagnostic: 45-55 years old



  • Splenomegaly (increased volume of the spleen)
  • Constitutional symptoms such as fatigue, fever, night sweats, anorexia and weight loss, anemia and recurring infections

Physiopathology (blood and bone marrow):

  • Increase leukocytes (granulocytosis)
  • Myélogramme avec cellularité riche et déviation de la lignée granulocytaire
  • Presence of the Philadelphia chromosome resulting a hybrid bcr/abl gene(Figure 1)
Chromosome philadelphie
CML is the result of an acquired somatic mutation (the Philadelphia chromosome) that fuses, through reciprocal chromosomal translocation, the bcr and abl genes on chromosomes 22 and 9, respectively. the resulting gene codes for a fusion protein with tyrosine kinase activity.


CML phases:

 CML phases eng

The initial CP of the disease, in which there may be no symptoms, presents in about 85% of patients with CML.  Prior to recent treatment advances, the CP lasted 5-6 years, the AP 6-9 months, and the BC 3-6 months.

CML treatment

Three approaches to treatment are known to exert a positive influence on the natural history of the disease:

  1. Allogeneic hematopoietic stem-cell transplantation (AHSCT)
  2. Interferon alpha (IFN-α) alone or in combination with low-dose cytarabine
  3. Tyrosine kinase inhibitors (TKI)

Stem-cell transplantation

To this day, it is the only treatment that offers the only prospect for the cure of CML. In general, the best results are obtained in CP with approximately 80% long-term remission. Despite its effectiveness, only about 25% of CML patients are eligible for the procedure, owing to age restrictions, absence of suitable donors, and the higher incidence of graft-versus-host disease.

Interferon alpha (IFN-α)

Therapy with interferon alpha is most effective in early-phase CP-CML.  Although IFN-a has expanded the therapeutic options for patients who are ineligible for transplant, the treatment has its shortcomings. Treatment for one or more years is required to establish the presence and degree of cytogenetic response, due to the slow kinetics of the biological response. For more than 50% of patients, side-effects related to IFN-a are intolerable and require dose reduction, while up to 25% discontinue treatment due to severe adverse effects.

Tyrosine kinase inhibitors (TKI)

The introduction of TKI in 2001 produces a drastic change in the clinical management of CML. TKI inhibits the bcr/abl tyrosine kinase and the proliferation of leukemic cells. Imatinib mesylate (Gleevec®), approved in first line by Health Canada in 2003, has profoundly altered the clinical and laboratory management of CML by becoming the standard of care and led the way to the development of more potent and selective second and third generation TKIs such as nilotinib (Tasigna®), dasatinib (Sprycel®), bosutinib (Bosulif®) and ponatinib (Iclusig®).


To help hematologists in their choice of treatment options, please visit the “Treatment guidelines” section to view the recommendations of the CML-MPN Quebec Research Group.