Differentiating AML from CML on CBC
CML presents with marked leukocytosis (often >100 × 10⁹/L) with a full spectrum of myeloid maturation including metamyelocytes, myelocytes, and promyelocytes, basophilia, and typically preserved or elevated platelets, while AML shows variable white counts with circulating blasts, cytopenias (anemia and thrombocytopenia), and lacks the orderly maturation seen in CML. 1, 2
CML CBC Picture
White Blood Cell Characteristics
- Extreme leukocytosis is the hallmark, frequently exceeding 100 × 10⁹/L 3
- Complete myeloid maturation spectrum present: predominantly metamyelocytes, myelocytes, and segmented forms, with few or occasional myeloblasts (<5%) 1
- Basophilia is characteristic and diagnostically important 1
- Eosinophils may be prominent 1
Other CBC Features
- Thrombocytosis is frequent - platelets often elevated or preserved 1, 3
- Severe anemia is rare at presentation 1
- Leukostatic symptoms (priapism, dyspnea, confusion) are uncommon despite extreme WBC counts 1
AML CBC Picture
White Blood Cell Characteristics
- Variable WBC count - can be low, normal, or elevated (not typically as extreme as CML) 2
- Circulating blasts are common, though blast percentage varies 1
- Lack of orderly myeloid maturation - no full spectrum of maturing granulocytes 1
- Blasts must comprise ≥20% of bone marrow cells for diagnosis (with exceptions for specific cytogenetic abnormalities) 1
Other CBC Features
- Cytopenias are typical: anemia and thrombocytopenia from bone marrow failure 2
- Neutropenia with leukocyte dysfunction leads to infections 2
- Easy bleeding/bruising from thrombocytopenia and platelet dysfunction 2
Clinical Presentation Differences
CML Presentation
- Often asymptomatic - approximately 40% diagnosed incidentally on routine blood work 1
- Massive splenomegaly with hepatomegaly when symptomatic 3
- Constitutional symptoms (weight loss, fatigue, sweats) are non-specific and less prominent 1
- Symptoms from splenomegaly (left upper quadrant fullness/pain) 1
AML Presentation
- Symptomatic at presentation - fatigue, bleeding, and fever are most common 2
- Splenomegaly and hepatomegaly are less common (unlike CML) 2
- Lymphadenopathy in approximately 20% 2
- Severe constitutional symptoms including fever, night sweats, weight loss 2
Confirmatory Testing Required
For CML
- BCR-ABL1 testing is mandatory - either by FISH or RT-PCR to confirm diagnosis before initiating therapy 1, 3
- Cytogenetics showing t(9;22)(q34;q11) Philadelphia chromosome 1
- Bone marrow shows hypercellularity with granulocytic proliferation, blasts <5%, and characteristic "dwarf megakaryocytes" 1
For AML
- Bone marrow aspirate showing ≥20% myeloblasts (or specific cytogenetic abnormalities regardless of blast count) 1
- Cytogenetics and molecular testing for risk stratification 1
- BCR-ABL1 must be negative to exclude CML 1
- Immunophenotyping by flow cytometry for lineage determination 1
Critical Pitfall to Avoid
Never rely solely on CBC to differentiate these entities - while the CBC patterns are highly suggestive, molecular confirmation with BCR-ABL1 testing is essential because CML in blast crisis can mimic AML, and both require fundamentally different treatment approaches (tyrosine kinase inhibitors for CML vs. intensive chemotherapy for AML) 1, 3. The presence of BCR-ABL1 fusion definitively establishes CML diagnosis and directs therapy toward TKI treatment rather than standard AML chemotherapy 3.