Acute Leukemias - Blast Off Basics
- Malignant clonal proliferation & accumulation of immature hematopoietic cells (blasts) in bone marrow.
- Blasts replace normal marrow elements, causing marrow failure.
- Key diagnostic criterion: >20% blasts in bone marrow (WHO).
- Main types:
- Acute Myeloid Leukemia (AML)
- Acute Lymphoblastic Leukemia (ALL)
- Presents with pancytopenia: fatigue, infections, bleeding.
⭐ The >20% blast count in bone marrow is a cornerstone for diagnosing acute leukemia according to WHO.
AML - Myeloid Mayhem
- Clonal proliferation of myeloblasts; ≥ 20% in bone marrow or peripheral blood.
- Hallmark: Auer rods (abnormal lysosomal granules).
Key WHO AML Genetic Subtypes:
| Category | Genetics | Morphology Highlights | Cyto |
|---|---|---|---|
| AML, t(8;21) | RUNX1-RUNX1T1 | Auer rods, dysplastic Eos | MPO+ |
| AML, inv(16) | CBFB-MYH11 | Abnormal Eos precursors | MPO+ |
| APL, t(15;17) | PML-RARA | Bundled Auer rods | MPO+++ |
| AML, KMT2A-r | e.g., t(9;11) | Monocytic features | NSE+ |
- Myeloperoxidase (MPO): Myeloid lineage.
- Sudan Black B (SBB): Myeloid (lipids).
- Non-Specific Esterase (NSE): Monocytic lineage (M4, M5).
- Periodic Acid-Schiff (PAS): M6 (block +ve), M7 (diffuse +ve).
- 📌 M3 APL: t(15;17) → 15+17=32, reverse 23 (M3).
⭐ Auer rods (needle-like cytoplasmic granules) are pathognomonic for AML, especially prominent in Acute Promyelocytic Leukemia (APL/M3).
ALL - Lymphoid Lightning
Acute Lymphoblastic Leukemia (ALL): Malignant proliferation of lymphoblasts (B or T lineage). Most common childhood cancer. Blasts >20% in marrow. PAS (+), TdT (+), MPO (-).
-
Clinical Features: Pancytopenia, bone pain, hepatosplenomegaly (HSM), lymphadenopathy (LAD).
-
B-ALL vs T-ALL Comparison:
Feature B-ALL (~85%) T-ALL (~15%) Markers CD19, CD10, PAX5, TdT CD2, CD3, CD7, TdT Key Genetics t(12;21) (good), t(9;22) (poor), Hyperdiploidy NOTCH1 mut. Clinical Younger kids, CNS/testes risk Teen males, Thymic mass, ↑WBC, SVC syndrome
📌 T-ALL: Thymic mass, Teens, Terrible prognosis (historically).
⭐ Prophylactic CNS therapy is crucial in ALL due to its propensity for central nervous system relapse.
Leukemia Dx - Detective Workup
- Initial: Peripheral Smear (PS) & Bone Marrow (BM) exam for morphology, blast count (>20%).
- Cytochemistry: Initial lineage determination.
Stain AML ALL Key Feature MPO/SBB + - Myeloid marker PAS Variable Block + Lymphoid (esp. ALL) TdT - + Lymphoblast marker - Immunophenotyping: Lineage (Myeloid/Lymphoid) & specific markers.
- Genetics: Karyotype, FISH (e.g., t(15;17) for APL), PCR/NGS for mutations.
⭐ Flow cytometry is indispensable for lineage assignment (myeloid vs lymphoid) and subtyping of acute leukemias.
Prognosis & Complications - Future Foretold
AML Prognosis
| Feature | Good | Poor |
|---|---|---|
| Cytogenetics | t(8;21), inv(16), t(15;17) | Complex, t(9;22), inv(3) |
| Molecular | NPM1 (no FLT3-ITD), CEBPA | FLT3-ITD, TP53 |
| Other | <60y, ↓WBC | >60y, ↑WBC, t-AML |
| Feature | Good | Poor |
| --------------- | --------------------------------------- | ----------------------------------------------- |
| Age/WBC | 1-9y, <50K/µL | <1y/>10y, >50K/µL(B)/>100K/µL(T) |
| Cytogenetics | Hyperdiploidy, t(12;21) | Hypodiploidy, t(9;22), KMT2A |
| Other | Rapid response | CNS disease, slow response |
- Tumor Lysis Syndrome (TLS)
- DIC (esp. APL)
- Neutropenic Sepsis
- Leukostasis (WBC >100,000/µL)
⭐ FLT3-ITD mutation in AML is a significant adverse prognostic marker.
High‑Yield Points - ⚡ Biggest Takeaways
- Acute leukemias are defined by >20% blasts in bone marrow.
- ALL is common in children, TdT+, PAS+, and has CNS/testicular sanctuary sites.
- AML is common in adults, MPO+, and may show Auer rods.
- APL (M3 AML) is associated with t(15;17), DIC, and responds to ATRA.
- Down syndrome increases risk of both ALL and AML.
- Gum hypertrophy is seen in AML M4/M5 (monocytic variants).
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