Acute Leukemia Lecture

Jun 20, 2024

Lecture Notes on Acute Leukemia

Hematopoietic Stem Cells

  • Hematopoietic stem cells can differentiate into:
    • Myeloid stem cells
      • Red blood cells
      • Monocytes
      • Granulocytes
      • Megakaryocytes
    • Lymphoid stem cells
      • B cells
      • T cells
  • Blasts: precursor cells
    • Myeloid blasts
    • Lymphoid blasts

Acute Leukemia Basics

  • In acute leukemia, cells lose the ability to differentiate/mature
  • Results in a buildup of blasts in the bone marrow
  • Normal blast cell count in bone marrow: 1-2%
  • Acute leukemia is defined by >20% blast cells in the bone marrow
  • Symptoms arise from loss of normal cells:
    • Anemia (fatigue)
    • Thrombocytopenia (bleeding issues)
    • Neutropenia (infections)
  • Rapid onset of symptoms

Diagnosis

  • Blood smear indicators:
    • Large immature cells with low cytoplasm
  • Identifying blast types:
    • Lymphoid blasts: Positive nuclear staining for TDT (DNA polymerase)
    • Myeloid blasts: Presence of myeloperoxidase (MPO, enzyme)
    • Auer rods: Crystallized form of MPO in myeloid blasts

Acute Lymphoblastic Leukemia (ALL)

  • B-cell ALL (B-ALL):
    • Common markers: CD10, CD19, CD20
    • Treatment: Chemotherapy
    • Additional prophylactic treatment for CNS and testes (blood-brain and blood-testes barriers)
    • Prognosis based on cytogenetics:
      • Good: t(12;21) translocation (common in children)
      • Poor: t(9;22) translocation (Philadelphia chromosome, common in adults)
  • T-cell ALL (T-ALL):
    • Common markers: Range from CD2 to CD8
    • Lack of CD10
    • Presents as a thymic mass (mediastinal mass) in teenagers (note mnemonic: T for thymus and T for teens)
    • Termed as acute lymphoblastic lymphoma due to mass formation

Acute Myeloid Leukemia (AML)

  • Indicators:
    • Myeloperoxidase (with Auer rods)
  • Common in adults (ages 50-60)
  • Subclassification:
    • Cytogenetic abnormalities (e.g. acute promyelocytic leukemia)
    • Lineage of myeloid blasts
    • Surface markers

Subtypes of AML

  • Acute Promyelocytic Leukemia (APL):
    • t(15;17) translocation disrupting retinoic acid receptor
    • Treatment: All-trans-retinoic acid (ATRA)
    • Risk of disseminated intravascular coagulation (DIC) due to Auer rods
  • Acute Monocytic Leukemia:
    • Lacks myeloperoxidase
    • Symptoms: Gum infiltration (swollen gums)
    • Subtypes include erythroblastosis and monoblast AML
  • Acute Megakaryoblastic Leukemia:
    • Association with Down syndrome (before age 5)
    • Lack of myeloperoxidase

Myelodysplastic Syndrome (MDS)

  • Characterized by abnormal buildup of blasts (<20%) in bone marrow
  • Leads to cytopenias (low blood cell count)
    • Symptoms: Infection, bleeding
  • Potential progression to AML if blasts >20%