Acute Leukemias

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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.

Normal vs AML bone marrow with increased blasts

⭐ 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).

MPO stain in AML blasts at diagnosis and relapse

Key WHO AML Genetic Subtypes:

CategoryGeneticsMorphology HighlightsCyto
AML, t(8;21)RUNX1-RUNX1T1Auer rods, dysplastic EosMPO+
AML, inv(16)CBFB-MYH11Abnormal Eos precursorsMPO+
APL, t(15;17)PML-RARABundled Auer rodsMPO+++
AML, KMT2A-re.g., t(9;11)Monocytic featuresNSE+
  • 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:

    FeatureB-ALL (~85%)T-ALL (~15%)
    MarkersCD19, CD10, PAX5, TdTCD2, CD3, CD7, TdT
    Key Geneticst(12;21) (good), t(9;22) (poor), HyperdiploidyNOTCH1 mut.
    ClinicalYounger kids, CNS/testes riskTeen males, Thymic mass, ↑WBC, SVC syndrome

📌 T-ALL: Thymic mass, Teens, Terrible prognosis (historically).

ALL lymphoblasts with PAS positive granules

⭐ 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.
    StainAMLALLKey Feature
    MPO/SBB+-Myeloid marker
    PASVariableBlock +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 CD45 vs SSC plot with cell populations

Flow cytometry is indispensable for lineage assignment (myeloid vs lymphoid) and subtyping of acute leukemias.

Prognosis & Complications - Future Foretold

AML Prognosis

FeatureGoodPoor
Cytogeneticst(8;21), inv(16), t(15;17)Complex, t(9;22), inv(3)
MolecularNPM1 (no FLT3-ITD), CEBPAFLT3-ITD, TP53
Other<60y, ↓WBC>60y, ↑WBC, t-AML
FeatureGoodPoor
-----------------------------------------------------------------------------------------------------
Age/WBC1-9y, <50K/µL<1y/>10y, >50K/µL(B)/>100K/µL(T)
CytogeneticsHyperdiploidy, t(12;21)Hypodiploidy, t(9;22), KMT2A
OtherRapid responseCNS 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).

Practice Questions: Acute Leukemias

Test your understanding with these related questions

What is the most common cell origin of acute lymphoblastic leukemia (ALL) in children?

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Flashcards: Acute Leukemias

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NPM1 and CEBPA mutation is associated with a _____ prognosis in patients with acute myeloid leukemia (AML).

TAP TO REVEAL ANSWER

NPM1 and CEBPA mutation is associated with a _____ prognosis in patients with acute myeloid leukemia (AML).

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