Leukemia
A 50-year-old man presents with fatigue, night sweats, and abdominal fullness. Examination
reveals massive splenomegaly. His blood work shows markedly elevated white blood cells with
myeloid precursors at all stages. A 25-year-old with fever and bruising has blast cells in blood
and bone marrow.
Sub-questions:
1. Define leukemia.
2. How is leukemia classified?
3. For chronic myeloid leukemia (CML), what are the peripheral blood smear and bone
marrow findings?
4. For acute leukemia, what is the FAB classification?
5. What are the cytochemical stains and laboratory findings?
Answers -:
1. Define : Leukemia is a malignant disease of the bone marrow stem cell characterized by:
• Bone marrow: Diffuse replacement with proliferating neoplastic blast cells that fail to
mature (blasts >20% of nucleated marrow cells by WHO criteria)
• Peripheral blood: Abnormal numbers and forms of immature white blood cells
Leukemia arises in the bone marrow and spreads to the peripheral blood and other tissues.
Note: "Aleukemic leukemia" refers to very few or no blasts in peripheral blood despite marrow
involvement.
2. Classification of Leukemiam-:
Traditional Classification
Type
Subtype
Acute leukemia
Acute myelogenous/myeloblastic leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Chronic leukemia
Chronic myeloid leukemia (CML)
Chronic lymphocytic leukemia (CLL)
FAB Classification of Acute Leukemias
Type
Subtype
Acute Lymphoid Leukemia (ALL)
L1 – Small homogeneous cells
L2 – Large cells, variable size
L3 – Large, homogeneous, vacuolated
Type
Subtype
Acute Myeloid Leukemia (AML)
M0 – Minimally differentiated AML
M1 – AML without maturation
M2 – AML with maturation
M3 – Promyelocytic leukemia
M4 – Myelomonocytic leukemia
M5 – Monocytic leukemia
M6 – Erythroleukemia
M7 – Megakaryocytic leukemia
3. Chronic Myeloid Leukemia (CML) – Findings :A. Peripheral Blood Findings
Parameter
Finding
Hemoglobin
Usually <11 g/dL (normocytic normochromic anemia)
Total leukocyte count
Markedly increased (12–600 × 10⁹/L); often >100 × 10⁹/L
Differential count
Shift to left – granulocytes at all stages (neutrophils, metamyelocytes, myelocytes,
promyelocytes, occasional myeloblasts)
Predominant cells
Neutrophils and myelocytes (“myelocyte bulge”)
Basophilia and
eosinophilia
Characteristic finding
Blasts
Usually <10% (chronic phase)
Platelets
Normal to increased (thrombocytosis common)
LAP/NAP score
Markedly reduced (<20; normal 40–100) – helps differentiate from leukemoid reaction
B. Bone Marrow Findings
Feature
Finding
Cellularity
Markedly hypercellular
Feature
Finding
M:E ratio
Often exceeds 20:1 (marked myeloid hyperplasia)
Erythropoiesis
Diminished as disease progresses
Myelopoiesis
Marked hyperplasia; blasts <10% (chronic phase)
Megakaryocytes
Normal or increased; dwarf megakaryocytes
Other
Sea-blue histiocytes (pseudo-Gaucher cells)
C. Cytogenetic Finding
· Philadelphia (Ph) chromosome – balanced reciprocal translocation t(9;22)(q34;q11.2)
· Results in BCR-ABL1 fusion gene → constitutively active tyrosine kinase → uncontrolled proliferation and
reduced apoptosis
5. Cytochemical Stains and Laboratory Findings in Acute Leukemia:A). Cytochemical Stains
Stain
Principle
AML Finding
ALL Finding
Myeloperoxidase
(MPO)
Oxidizes dye substrate
in myeloid granules
Positive (myeloblasts)
Negative
Sudan Black B (SBB)
Stains
lipids/phospholipids in
myeloid granules
Positive (similar to MPO)
Negative
Nonspecific
esterase (NSE)
Stains monocytic cells
Positive in M4 and M5
(monocytic component)
Negative
Periodic acid-Schiff
(PAS)
Stains glycogen
Myeloblasts negative;
erythroblasts positive
(M6)
Block positivity
(coarse granular)
in lymphoblasts
Alkaline phosphatase
in mature neutrophils
Decreased in AML?
Actually LAP is
decreased in CML,
variable in AML. LAP
increased in leukemoid
reaction.
Normal or
variable
Neutrophil alkaline
phosphatase
(NAP/LAP)
B). Laboratory Findings in Acute Leukemia
Parameter
Finding
Hemoglobin
Decreased (normocytic normochromic anemia)
Platelet count
Decreased (thrombocytopenia)
Total WBC count
Variable (may be high, normal, or low – aleukemic)
Peripheral smear
Blasts ≥20% (WHO); presence of Auer rods (AML, especially M2/M3)
Bone marrow
Hypercellular with >20% blasts; suppression of normal hematopoiesis
Serum uric acid
Raised (due to increased cell turnover)
Serum LDH
Raised
C). Specific for AML-M3 (Acute Promyelocytic Leukemia)
· Auer rods are abundant (often multiple, faggot cells)
· Associated with DIC (disseminated intravascular coagulation) due to release of procoagulants
· t(15;17)(q22;q12) – PML-RARA fusion
D). Specific for ALL-L3 (Burkitt type)
· Oil red O stain positive (vacuoles contain lipid)
· Surface immunoglobulin positive
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