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Chronic Myeloid Leukemia (CML)

Chronic Myeloid Leukemia (CML) is a chronic myeloproliferative neoplasm (MPN) characterized by the uncontrolled proliferation of mature and maturing myeloid cells, driven by the BCR-ABL1 fusion gene (Philadelphia chromosome)

Also called

Chronic Myelogenous Leukemia

ICD-10

C92.1

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Chronic Myeloid Leukemia (CML) is caused by the Philadelphia chromosome, resulting from the t(9;22) translocation, which creates the BCR-ABL1 fusion gene. This abnormal tyrosine kinase causes uncontrolled proliferation of myeloid cells. Most patients present in the chronic phase, and modern tyrosine kinase inhibitors (TKIs) have dramatically improved survival.

Etiology & Risk Factors

-Etiology of Chronic Myeloid Leukemia (CML)

Chronic Myeloid Leukemia (CML) is caused by an acquired reciprocal translocation:

  • t(9;22)(q34;q11)

This creates the:

  • BCR-ABL1 fusion gene

The fusion protein has constitutively active tyrosine kinase activity.

-Risk Factors

  • Increasing age

  • Male sex

  • Previous exposure to ionizing radiation

  • Rare familial predisposition

Pathophysiology

Acquired t(9;22) translocation → formation of the BCR-ABL1 fusion gene → constitutive tyrosine kinase activation → uncontrolled proliferation of myeloid stem cells → excessive production of granulocytes and their precursors → accumulation in bone marrow, blood, and spleen → progressive disease through chronic, accelerated, and blast phases if untreated

Clinical Presentation

-Symptoms

  • Fatigue

  • Weight loss

  • Night sweats

  • Fever

  • Early satiety

  • Abdominal fullness

  • Left upper quadrant pain

  • Bone pain

-Signs

  • Splenomegaly (common)

  • Hepatomegaly

  • Pallor

  • Bruising

  • Petechiae (advanced disease)

Disease Phases:

-Chronic Phase

  • Often asymptomatic

  • Mild constitutional symptoms

  • Marked leukocytosis

-Accelerated Phase

  • Increasing symptoms

  • Progressive splenomegaly

  • Worsening cytopenias or thrombocytosis

  • Rising blast count

-Blast Phase

  • Resembles acute leukemia

  • Severe infections

  • Bleeding

  • Bone marrow failure

History Taking

-Ask about:

  • Fatigue
  • Weight loss
  • Night sweats
  • Fever
  • Abdominal discomfort
  • Early satiety
  • Bleeding
  • Bone pain
  • Previous radiation exposure
  • Family history
  • Symptoms suggesting disease progression

Physical Examination

-General Examination

Look for:

  • Pallor

  • Weight loss

  • Fever

  • Bruising

-Abdominal Examination

Assess for:

  • Splenomegaly

  • Hepatomegaly

-Additional Examination

Look for:

  • Petechiae

  • Signs of anemia

  • Signs of blast crisis

Investigations

-Complete Blood Count (CBC)

Typical findings:

  • Marked leukocytosis

  • Left shift with myeloid precursors

  • Basophilia

  • Eosinophilia

  • Mild anemia

  • Platelet count may be increased

-Peripheral Blood Film

Characteristic findings:

  • Marked granulocytosis

  • Myelocytes

  • Metamyelocytes

  • Promyelocytes

  • Basophilia

  • Eosinophilia

  • Few blasts (<10% in chronic phase)

-Bone Marrow Aspiration and Biopsy

Typical findings:

  • Hypercellular marrow

  • Marked granulocytic hyperplasia

  • Increased myeloid-to-erythroid ratio

-Cytogenetic Testing

  • Philadelphia chromosome [t(9;22)]

-Molecular Testing (Gold Standard)

  • BCR-ABL1 detection by quantitative PCR (qPCR)

  • Fluorescence in situ hybridization (FISH) when indicated

-Additional Investigations

  • LDH

  • Uric acid

  • Liver function tests

  • Renal function tests

  • Bone marrow cytogenetics

  • ECG and echocardiography before selected TKIs if indicated

Diagnosis

-Diagnosis of Chronic Myeloid Leukemia (CML) is based on:

    • CBC and peripheral blood film
    • Bone marrow examination
    • Detection of the Philadelphia chromosome
    • Identification of the BCR-ABL1 fusion gene by PCR or FISH
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Related Topics

Management

-First-Line Treatment

Tyrosine Kinase Inhibitors (TKIs)

  • Imatinib

  • Dasatinib

  • Nilotinib

  • Bosutinib

  • Asciminib (selected patients)

-Monitoring

  • Regular CBC

  • Quantitative BCR-ABL1 PCR every 3 months initially

  • Assess molecular response and treatment adherence

-Resistant or Advanced Disease

  • Switch to an alternative TKI based on mutation profile

  • Allogeneic hematopoietic stem cell transplantation for selected patients

  • Blast phase treated similarly to acute leukemia plus TKI therapy

-Supportive Care

  • Hydration

  • Management of hyperuricemia

  • Blood transfusions if required

  • Infection management

Complications

  • Accelerated phase
  • Blast crisis
  • Severe anemia
  • Infection
  • Bleeding
  • Hyperuricemia
  • Splenic infarction (rare)
  • Treatment resistance

Prognosis

The prognosis has improved dramatically with tyrosine kinase inhibitor therapy. Most patients diagnosed in the chronic phase achieve long-term disease control and near-normal life expectancy. Poor prognosis is associated with progression to accelerated or blast phase, inadequate molecular response, or resistant BCR-ABL1 mutations

Key Points / Clinical Pearls

  • Chronic Myeloid Leukemia (CML) is a BCR-ABL1-positive myeloproliferative neoplasm.
  • It is caused by the Philadelphia chromosome [t(9;22)].
  • Patients commonly present with marked leukocytosis and splenomegaly.
  • Peripheral blood shows all stages of granulocyte maturation with basophilia.
  • BCR-ABL1 PCR is the key diagnostic and monitoring test.
  • Imatinib and other TKIs are first-line therapy.
  • Molecular monitoring with quantitative PCR is essential during follow-up.
  • CML progresses through chronic, accelerated, and blast phases if untreated.
  • Allogeneic stem cell transplantation is reserved for selected resistant or advanced cases.
  • With modern TKI therapy, most patients have an excellent long-term prognosis.