Leukemias are hematologic malignancies characterized by clonal proliferation of hematopoietic precursor cells. They are classified by the lineage of the involved cells (myeloid or lymphoid) and the clinical course (acute — rapid progression, or chronic — indolent progression). Laboratory diagnosis integrates the CBC, peripheral blood smear, bone marrow examination, flow cytometry, and cytogenetic/molecular studies.
Acute Myeloid Leukemia (AML)
AML is the most common acute leukemia in adults (median age 68 years), characterized by clonal expansion of myeloid blasts in the bone marrow or blood. Blasts must be ≥ 20% of nucleated cells in blood or bone marrow, except for specific recurrent genetic abnormalities (t(15;17), t(8;21), inv(16), t(9;11)) which define AML regardless of blast percentage. The CBC typically shows anemia, thrombocytopenia, and variable WBC count (leukopenia to marked leukocytosis). Blasts are present on the blood smear in most cases. Cytochemical stains: myeloperoxidase (MPO) and Sudan black B are positive in myeloid blasts (≥ 3% positive). Non-specific esterase (NSE) positivity inhibited by fluoride is characteristic of monocytic differentiation. Flow cytometry shows positivity for CD13, CD33, CD117, and MPO, with variable CD34, HLA-DR, CD11b, and CD14 expression.
WHO classification includes AML with recurrent genetic abnormalities (t(8;21), inv(16)/t(16;16), t(15;17), t(9;11), t(6;9), inv(3)/t(3;3), t(1;22), NPM1 mutation, CEBPA biallelic mutation, KMT2A rearrangement), AML with myelodysplasia-related changes, therapy-related AML, AML not otherwise specified (subtypes M0–M7 by FAB), and myeloid sarcoma (extramedullary tumor of blasts). Acute promyelocytic leukemia (APL, t(15;17) PML-RARA) is a medical emergency due to DIC risk and requires urgent ATRA therapy.
Acute Lymphoblastic Leukemia (ALL)
ALL is the most common childhood malignancy (peak incidence 2–5 years) but also occurs in adults. B-ALL comprises approximately 75% of pediatric and 80% of adult cases. T-ALL accounts for 15–20% of pediatric and 25% of adult cases and presents more frequently with a mediastinal mass. The CBC is variable: WBC may be low, normal, or markedly elevated. Blasts in the blood or bone marrow ≥ 20% (≥ 25% by older FAB criteria). Flow cytometry: B-ALL is positive for CD19, CD22, CD79a, PAX5, and TdT; with immature markers (CD34, CD10) varying by subtype. T-ALL is positive for cytoplasmic CD3, CD7, CD2, CD5, and TdT. Cytogenetic subgroups carry distinct prognoses: hyperdiploidy (> 50 chromosomes) and t(12;21) ETV6-RUNX1 are favorable; hypodiploidy, t(9;22) BCR-ABL1 (Ph+), KMT2A rearrangements, and iAMP21 are high-risk.
Chronic Myeloid Leukemia (CML)
CML is a myeloproliferative neoplasm driven by the BCR-ABL1 fusion protein (Philadelphia chromosome, t(9;22)). It has three phases. Chronic phase (85–90% at diagnosis): leukocytosis (WBC often > 50 × 10⁹/L, can exceed 500), with a full spectrum of myeloid maturation (segmented neutrophils, bands, metamyelocytes, myelocytes, promyelocytes, and rare blasts). Basophilia and eosinophilia are characteristic. Platelets are normal or increased. The LAP score is low. Accelerated phase: increasing blast count (10–19%), increasing basophilia, cytopenias, and clonal evolution. Blast phase: blasts ≥ 20%, resembling AML or ALL. Diagnosis is confirmed by detection of BCR-ABL1 by FISH or PCR. Tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) achieve deep molecular responses, and MRD monitoring by quantitative PCR is standard of care.
Chronic Lymphocytic Leukemia (CLL)
CLL is the most common leukemia in adults in Western countries (median age 72 years), characterized by clonal expansion of mature CD5+ B lymphocytes. Diagnosis requires ≥ 5 × 10⁹/L clonal B lymphocytes in blood persisting for > 3 months. The blood smear shows small lymphocytes with scant cytoplasm, clumped chromatin (soccer ball nuclei), and smudge cells (broken cells, a characteristic artifact of slide preparation). The CBC shows lymphocytosis with variable anemia and thrombocytopenia (progressive marrow infiltration or autoimmune cytopenias). Flow cytometry: CD5+, CD19+, CD23+, CD20 (dim), surface immunoglobulin (dim). CLL is staged by Rai or Binet systems. Monoclonal B-cell lymphocytosis (MBL) is a precursor state with < 5 × 10⁹/L clonal B cells and no cytopenias. Richter transformation (5–10% of CLL) converts to aggressive large B-cell lymphoma with poor prognosis.
Diagnostic Workflow
When blasts are detected on the blood smear or CBC flags indicate abnormal cells, reflex testing includes flow cytometry and cytogenetics. The distinction between AML and ALL is critical as treatment differs fundamentally. Cytochemical stains (MPO, NSE, PAS) provide rapid preliminary lineage assignment pending flow cytometry. The turnaround time for flow cytometry is typically 24–48 hours, with cytogenetic/FISH results in 2–7 days and molecular results in 5–14 days. Integration of all modalities is essential for WHO classification and treatment planning.
