Acute and chronic leukemias, myelodysplastic syndrome

Leukemias are clonal hematopoietic neoplasms involving bone marrow and blood. They are classified by:

  • Lineage: myeloid vs lymphoid
  • Course: acute vs chronic
  • Acute leukemias: rapid, accumulation of blasts (immature cells) → marrow failure
  • Chronic leukemias: slower, composed of more mature cells

Myelodysplastic syndrome (MDS) is a clonal stem cell disorder with ineffective hematopoiesis, cytopenias, dysplasia, and risk of transformation to AML.

Acute Leukemias

General Features

  • ≥20% blasts in marrow/blood (with exceptions for defining mutations)
  • Pathogenesis:
    • Mutation → ↑ proliferation + ↓ differentiation
    • → accumulation of nonfunctional blasts
  • Results:
    • ↓ RBC → anemia
    • ↓ platelets → bleeding
    • ↓ functional WBC → infections

Acute Lymphoblastic Leukemia (ALL)

Malignancy of lymphoid precursors (B or T cells)→ most common childhood leukemia

Pathogenesis

  • Genetic abnormalities (e.g. ETV6-RUNX1, hyperdiploidy, BCR-ABL1)
  • Block in lymphoid differentiation

Morphology & Markers

  • Small blasts, high N:C ratio
  • TdT+, MPO−
  • B-ALL: CD10, CD19
  • T-ALL: CD3

Clinical Features

  • Bone marrow failure (fatigue, infections, bleeding)
  • CNS + testicular involvement
  • T-ALL → mediastinal mass
  • Most curable leukemia (especially in children)
  • Requires CNS prophylaxis

Acute Myeloid Leukemia (AML)

Malignancy of myeloid precursors → mainly adults

Pathogenesis

  • De novo or secondary (MDS, chemo, radiation)
  • Mutations → impaired differentiation

Morphology & Markers

  • Larger blasts, prominent nucleoli
  • MPO+, TdT−
  • Auer rods (needle-like inclusions)

Important Subtype: APL

  • t(15;17) → PML-RARA
  • Risk of DIC

Clinical Features

  • Marrow failure + leukostasis (high WBC)
  • Prognosis depends on cytogenetics
  • Transplant = potentially curative

Chronic Leukemias

General Features

  • Slower progression
  • More differentiated cells
  • Often asymptomatic initially

Chronic Lymphocytic Leukemia (CLL)

Neoplasm of mature B cells → most common adult leukemia

Pathogenesis

  • Accumulation of long-lived B cells
  • Common mutations: del(13q), trisomy 12, TP53 loss

Morphology & Markers

  • Small lymphocytes + smudge cells
  • CD5+, CD19+, CD23+

Clinical Features

  • Often incidental finding
  • Lymphadenopathy, splenomegaly
  • Hypogammaglobulinemia → infections

Complications

  • Autoimmune hemolytic anemia
  • Richter transformation → aggressive lymphoma
  • Targeted therapy (BTK inhibitors)

Chronic Myeloid Leukemia (CML)

Myeloproliferative neoplasm with BCR-ABL1 fusion (Philadelphia chromosome)

Pathogenesis

  • Constitutive tyrosine kinase activation → uncontrolled proliferation

Phases

  1. Chronic phase (stable)
  2. Accelerated phase
  3. Blast crisis (resembles acute leukemia)

Clinical Features

  • Marked leukocytosis
  • Splenomegaly
  • Fatigue, weight loss

Diagnosis

  • Detect BCR-ABL1 (PCR/FISH)
  • Treated with tyrosine kinase inhibitors (imatinib)
  • Excellent prognosis in chronic phase

Myelodysplastic Syndrome (MDS)

Clonal stem cell disorder with:

  • Ineffective hematopoiesis
  • Cytopenias
  • Dysplasia in ≥1 lineage
  • Risk of AML transformation

Pathogenesis

  • Stem cell mutation → defective maturation
  • Marrow often hypercellular, but cells die early → “ineffective production”

Morphology

Blood

  • Cytopenias (anemia most common)

Bone Marrow Dysplasia

  • Erythroid: macrocytosis, ring sideroblasts
  • Granulocytic: hypogranular neutrophils, pseudo–Pelger-Huët
  • Megakaryocytes: small, abnormal nuclei

Classification

  • MDS with isolated del(5q) → good prognosis
  • MDS with SF3B1 mutation (ring sideroblasts)
  • MDS with TP53 mutation → poor prognosis

Clinical Features

  • Fatigue (anemia)
  • Infections (neutropenia)
  • Bleeding (thrombocytopenia)

Diagnosis

  • Persistent cytopenia
  • Dysplasia ≥10% cells
  • Blasts <20% (≥20% → AML)
  • Exclude B12/folate deficiency

Treatment

  • Supportive (transfusions, ESAs)
  • Hypomethylating agents (azacitidine)
  • Stem cell transplant = only cure


References

  1. AMBOSS – Acute and Chronic Leukemias, MDS
  2. Robbins & Cotran Pathologic Basis of Disease (10th ed.)
  3. WHO Classification of Tumours of Haematolymphoid Neoplasms (2022)
  4. Harrison’s Principles of Internal Medicine (Hematology sections)
  5. StatPearls (NCBI) – Acute Myeloid Leukemia, Myelodysplastic Syndromes