What are the typical laboratory findings in Chronic Myeloid Leukemia (CML)?

Typical Laboratory Findings in Chronic Myeloid Leukemia (CML)

The hallmark laboratory findings in CML include leukocytosis with left-shifted granulopoiesis, basophilia, eosinophilia, thrombocytosis, and the presence of the Philadelphia chromosome or BCR-ABL1 rearrangement. 1, 2

Key Hematologic Findings

Complete Blood Count (CBC) Abnormalities

• Leukocytosis: Often marked, with white blood cell counts frequently exceeding 100 × 10⁹/L 2
• Left-shifted granulocytosis: Presence of immature granulocytes at all stages of maturation (myelocytes, metamyelocytes, promyelocytes) 1
• Basophilia: Characteristic finding, often prominent 1, 2
• Eosinophilia: Common finding 1
• Thrombocytosis: Frequently observed 1, 2
• Mild anemia: May be present 2

Bone Marrow Findings

• Hypercellular bone marrow with granulocytic proliferation in various stages of maturation 2
• Blasts typically <5% in chronic phase 2
• Increased megakaryocytes may be present

Genetic/Molecular Findings

Cytogenetic Abnormalities

• Philadelphia (Ph) chromosome: Present in 85-90% of cases, resulting from the balanced translocation t(9;22)(q34;q11) 1
• Variant translocations: Present in 5-10% of cases, involving chromosomes 9,22, and additional chromosomes 1
• Cryptic BCR-ABL1 fusion: Present in 1-5% of cases without visible Ph chromosome 1

Molecular Markers

• BCR-ABL1 fusion gene: Definitive diagnostic marker, detectable by:
  • Fluorescence in situ hybridization (FISH) 1
  • Reverse transcriptase polymerase chain reaction (RT-PCR) 1
  • Quantitative RT-PCR (QPCR) for monitoring disease burden 1

Disease Phase Indicators

Chronic Phase (90% of newly diagnosed cases)

• Blasts <10% in blood or bone marrow 1, 3
• Basophils <20% in blood 1
• Platelet count normal or elevated (100-1000 × 10⁹/L) 3

Accelerated Phase

• 10-29% blasts in blood or bone marrow 1

• 20% basophils in blood 1

• Thrombocytosis or thrombocytopenia unrelated to therapy 1
• Clonal cytogenetic evolution 1

Blast Phase/Crisis

• ≥30% blasts in blood or bone marrow 1
• Extramedullary blastic infiltration 1

Biochemical Abnormalities

• Elevated uric acid levels (may lead to gouty arthritis) 2
• Elevated histamine levels (due to basophilia) 2
• Liver function tests may be normal or mildly elevated 4

Common Pitfalls in Laboratory Diagnosis

1. Missing the diagnosis in asymptomatic patients: About 40-50% of patients are asymptomatic at diagnosis, with CML discovered incidentally during routine blood tests 1, 2

2. Overlooking Ph-negative CML: In approximately 5% of cases, the Philadelphia chromosome cannot be detected by conventional cytogenetics, requiring molecular methods (FISH or RT-PCR) for diagnosis 1

3. Confusing with other myeloproliferative neoplasms: Atypical CML is BCR-ABL1 negative, lacks basophilia, and shows dysplasia of erythro-, granulo- and/or megakaryopoiesis 1

4. Inadequate monitoring: After diagnosis, regular monitoring with quantitative RT-PCR is essential to assess treatment response and detect early relapse 1

Monitoring Parameters During Treatment

• Complete hematologic response: Normalization of peripheral blood counts (leukocytes <10 × 10⁹/L, platelets <450 × 10⁹/L), absence of immature cells, and resolution of splenomegaly 1

• Molecular response: Measured by quantitative RT-PCR for BCR-ABL1 transcripts 1

  • Major molecular response (MMR): BCR-ABL1 transcripts ≤0.1% by QPCR
  • Complete molecular response: No detectable BCR-ABL1 mRNA

• BCR-ABL1 kinase domain mutation analysis: Indicated for inadequate response to therapy or disease progression 1

Remember that laboratory findings must be interpreted in the clinical context, and definitive diagnosis requires demonstration of the Philadelphia chromosome and/or BCR-ABL1 rearrangement in the appropriate clinical setting.