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Hematology

Myeloid Neoplasia

Overview of Myeloid Neoplasms

  • Definition: A group of hematologic malignancies originating from clonal hematopoietic stem cells or early progenitor cells of the myeloid lineage in the bone marrow
  • Key Characteristics:
    • Abnormal Proliferation: Uncontrolled growth of myeloid cells
    • Dysplasia: Abnormal cell maturation and morphology
    • Variable Differentiation: Some myeloid neoplasms primarily involve immature cells (blasts), while others involve more mature cells
    • Risk of Transformation: Many myeloid neoplasms can progress to acute myeloid leukemia (AML)
  • Classification: The World Health Organization (WHO) classification system is used to categorize myeloid neoplasms based on clinical, morphological, immunophenotypic, cytogenetic, and molecular features
  • General Categories:
    • Acute Myeloid Leukemia (AML)
    • Myelodysplastic Syndromes (MDS)
    • Myeloproliferative Neoplasms (MPNs)
    • Myeloid/Lymphoid Neoplasms with Eosinophilia and Defining Genetic Abnormalities
    • Myeloid Sarcoma

Acute Myeloid Leukemia (AML)

  • Definition: Aggressive hematologic malignancy characterized by the accumulation of ≥20% myeloid blasts in the bone marrow or peripheral blood
  • Pathophysiology:
    • Genetic mutations block myeloid differentiation, leading to a buildup of immature blasts
    • Blasts crowd out normal hematopoietic cells, causing cytopenias (anemia, thrombocytopenia, neutropenia)
  • Classification:
    • AML with Recurrent Genetic Abnormalities: AML with specific chromosomal translocations or gene mutations (e.g., AML with t(8;21), AML with t(15;17), AML with NPM1 mutation, AML with FLT3-ITD)
    • AML with Myelodysplasia-Related Changes: AML arising from or associated with a prior myelodysplastic syndrome
    • Therapy-Related AML: AML arising as a late complication of cytotoxic chemotherapy or radiation therapy
    • AML Not Otherwise Specified (AML-NOS): AML that does not meet the criteria for the other categories and is classified based on morphology and cytochemistry

Myelodysplastic Syndromes (MDS)

  • Definition: A group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplasia in one or more cell lines, and a variable risk of progression to AML
  • Pathophysiology:
    • Genetic mutations impair the differentiation and maturation of hematopoietic cells, leading to cytopenias and dysplasia
    • Dysplastic cells are prone to apoptosis (programmed cell death), contributing to ineffective hematopoiesis
  • Classification:
    • Based on morphological features, cytogenetic abnormalities, and blast percentage in the bone marrow and peripheral blood
    • Key subtypes include:
      • Refractory Anemia (RA)
      • Refractory Anemia with Ring Sideroblasts (RARS)
      • Refractory Cytopenia with Multilineage Dysplasia (RCMD)
      • Refractory Anemia with Excess Blasts (RAEB-1 and RAEB-2)
      • MDS with Isolated del(5q)

Myeloproliferative Neoplasms (MPNs)

  • Definition: A group of clonal hematopoietic stem cell disorders characterized by the overproduction of one or more myeloid cell lines in the bone marrow
  • Key Features:
    • Increased Blood Cell Counts: Elevated WBC count, RBC count, and/or platelet count
    • Splenomegaly: Enlargement of the spleen due to extramedullary hematopoiesis and increased workload
    • Risk of Thrombosis and Bleeding: Due to abnormal platelet function or elevated blood cell counts
    • Risk of Transformation: Can progress to myelofibrosis or acute leukemia
  • Classification:
    • Chronic Myeloid Leukemia (CML): Characterized by the presence of the BCR-ABL1 fusion gene
    • Polycythemia Vera (PV): Primarily involves increased RBC production; associated with the JAK2 V617F mutation
    • Essential Thrombocythemia (ET): Primarily involves increased platelet production; associated with mutations in JAK2, CALR, or MPL
    • Primary Myelofibrosis (PMF): Characterized by bone marrow fibrosis, splenomegaly, and extramedullary hematopoiesis; associated with mutations in JAK2, CALR, or MPL

General Laboratory Features

  • Complete Blood Count (CBC) with Differential: To assess the number and types of blood cells, as well as to assess for any abnormalities such as cytopenias or increased numbers of blasts
  • Peripheral Blood Smear: To evaluate the morphology of blood cells and identify any qualitative abnormalities (e.g., dysplasia)
  • Bone Marrow Aspiration and Biopsy: To assess the cellularity and morphology of the bone marrow, as well as to detect any dysplasia or abnormal cell populations
  • Cytogenetic Analysis: To identify chromosomal abnormalities, such as translocations, deletions, or inversions
  • Flow Cytometry: To identify cell surface markers and classify blood cells
  • Molecular Testing: To detect gene mutations (e.g., JAK2, CALR, MPL, FLT3, NPM1, CEBPA) and fusion genes (e.g., BCR-ABL1)

Key Terms

  • Myeloid Neoplasm: A hematologic malignancy arising from myeloid progenitor cells
  • Acute Myeloid Leukemia (AML): An aggressive leukemia with ≥20% blasts in the bone marrow or blood
  • Myelodysplastic Syndromes (MDS): A group of clonal bone marrow disorders characterized by ineffective hematopoiesis and dysplasia
  • Myeloproliferative Neoplasms (MPNs): A group of clonal bone marrow disorders characterized by the overproduction of one or more blood cell lines
  • Blast Cells: Immature, abnormal cells seen in acute leukemia
  • Dysplasia: Abnormal cell development or maturation
  • Cytopenia: Deficiency of blood cells (e.g., anemia, neutropenia, thrombocytopenia)
  • BCR-ABL1 Fusion Gene: A fusion gene created by the translocation between chromosomes 9 and 22, resulting in the Philadelphia chromosome (seen in CML)
  • JAK2 Mutation: A mutation in the JAK2 gene that is commonly found in MPNs
  • Phlebotomy: Removal of blood to reduce red cell mass