FT1

• Myelodysplastic Disorders


  Aka Pre-leukemias
• Leukemias


  Malignant neoplasm characterized by disorderly, purposeless & uncontrolled proliferation of one or more of the hematopoietic cells (BM)
• Leukemias


  Disease of blood-forming tissues, predominantly the BM
• Causes or Etiology of Leukemias

  • Genetic mutation
  • Oncogene activation
• Genetic mutation


  • There's a problem with a chromosome
  • Translocation: A part of chromosome breaks off and becomes attached to another chromosome
  • Deletion: Occur if a part of a chromosome is lost
• Oncogene


  • Aka cancer gene
  • Cancer activation happens when there is a problem when it comes to B-cell differentiation → Positive and Negative selection
• Implicated Conditions


  • Chromosomal Abnormalities
  • Familial incidence/hereditary
  • Chemical agents
  • Ionizing radiation
  • Immunological defects
  • Viruses (EBV & HTLV): Retrovirus I and II
• Chromosomal Abnormalities


  • Ph1 chromosome
  • Trisomy 21
  • Translocation of a part of chr 8-14
• Chemical agents


  Reagents that contain benzene or xylene → cause aplastic anemia
• Immunological defects


  • Breakdown of the immunosurveillance that normally keeps neoplastic growths in check
  • Especially seen in lymphocytic leukemia and lymphoma
• Cancerous cell clone in Leukemia

  • Grows rapidly and at the expense of normal hematopoietic cells
• Systemic Symptoms of Leukemia


  • Fatigue
  • Headache
  • Dizziness
  • Fever
  • Increase sweating
  • Bleeding problems
• Hypermetabolism in Leukemia


  Patients have fast metabolism → slim
• Classification of Leukemias


  • Cell Line: Myeloid Leukemia, Lymphoid Leukemia
  • % of blasts in PB and BM: Acute Leukemia, Chronic Leukemia, Sub-acute Leukemia
  • Number of WBCs in the PB
  • FAB Classification (1976)
  • WHO (1997)
• Blast


  Immature cell
• Acute Leukemia


  • With increased blast cells in the BM and PB
  • FAB Criteria: >30% BM blasts
  • WHO criteria: ≥20% BM blasts
  • Prognosis: Rapidly progressive, Days to 6 months, Shorter prognosis
• Chronic Leukemia


  • Less than 10% blasts in PB
  • Less than 30% in BM blast
  • Prognosis: 1-2 years or more, Better and longer prognosis
• Sub-acute Leukemia


  • Chronic transforming into acute
  • 10-30% blast in the PB + other s/s
  • Prognosis: 2-6 months
• Leukemic Leukemia


  WBC count is more than 15,000/uL
• Sub-leukemic Leukemia


  • WBC count is less than 15,000/uL
  • Presence of immature or abnormal cells in the PB
• Aleukemic Leukemia


  • WBC count is less than 15,000/uL
  • No immature nor abnormal cells in the PB
• FAB Classification (1976)


  Morphology and cytochemical stains characteristics
• WHO (1997)


  Cellular morphology, cytochemical stains, immunologic probes of cell markers, cytogenic abnormalities and clinical syndrome
• FAB & WHO: standardized classification of leukemia
• Acute Myelocytic Leukemia (AML)/ Acute Non-lymphocytic Leukemia


  • Stem cell disorder with predominance of blast cells (≥20%) in the blood or marrow
  • Most common form of acute leukemia during the first few months of life
  • May resemble acute infection at presentation
  • Incidence or Common In: Newborns, Adults (>60 years)
  • Causes: Ionizing radiation, Leukomogens, Congenital Factors/ Genetic, Viruses, Neoplasia
  • Treatment: Chemotherapy, Radiotherapy, Bone marrow transplant, Differentiation Treatment (ATRA), Supportive Management
• Key Myeloid Ag

  • CD13
  • CD33
  • CD117
  • CD14/CD64
• Primitive Myeloblasts

  • Myeloid associated antigens: MPO, CD13, CD33, CD117
• More mature myeloblasts

  • Cytochemical: MPO, SBB, CAE
• AML/ANLL (WHO CLASSIFICATION)


  • AML with recurrent cytogenic abnormalities
  • AML with multilineage dysplasia
  • AML, Therapy related: alkylating agents or radiation
  • AML, not otherwise classified
• FAB CLASSIFICATION (AML NOT OTHERWISE CLASSIFIED)

  • M0: AML with minimal differentiation/ undifferentiated leukemia
  • M1: Acute myeloblastic L. without maturation
  • M2: Acute myeloblastic L. with maturation
  • M3: Acute Promyelocytic L. (Hypergranular promyelocytic leukemia)
  • M4: Acute Myelomonocytic L. ("Naegeli" monocytic L.)
  • M5: Acute Monocytic L (Schilling's Leukemia)
  • M6: Erthroleukemia/Erythremic myelosis (DiGuglielmo Disease, Pure Erythroid Leukemia)
  • M7: Acute megakaryocytic L
• Stains for FAB Classification

  • MPO: myeloperoxidase
  • SBB: Sudan Black B
  • ANCAE: alpha-naphthyl chloroacetate esterase
  • a-naphthyl acetate (& butyrate) esterase
  • Periodic Acid Schiff (PAS)
• M0 (AML with minimal differentiation/ undifferentiated leukemia)


  (-) with all cytochemical stains
• M1 (Acute myeloblastic L. without maturation)


  >30% myeloblast

  Auer rods
• M2 (Acute myeloblastic L. with maturation)

  • >30% myeloblast with
  • >10% granulocytic component (Promyelocyte to neutrophils)
  • Auer rods
  • WHO: T(8:21)
• M3 (Acute Promyelocytic L.) (Hypergranular promyelocytic leukemia)

  • With heavy granulation
  • Many Auer rods in bundles called faggot cells (3 or more Auer rods)
  • Associated with DIC (Simultaneous fibrinolysis and coagulation)
  • WHO: T(15:17)
• M4 (Acute Myelomonocytic L.) (“Naegeli” monocytic L.)

  • >20% of PB WBCs are monocytes or monocytic precursors
  • WHO: Inv(16)
• M5 (Acute Monocytic L) (Schilling’s Leukemia)

  • >80% BM elements are of monocytic series
  • WHO: T(9:11)
• M6 (Erthroleukemia/Erythremic myelosis) (DiGuglielmo Disease) (Pure Erythroid Leukemia)

  • With neoplastic myeloblasts and erythroblasts
  • >50% are erythroid cells in all stages of maturation
• M7 (Acute megakaryocytic L)

  • Predominantly megakaryoblasts, micromegakaryoblasts (≥30%)
  • Affected are: platelets
• M5a

  • Poorly differentiated monocytic leukemia
  • Predominant cell is: promonocyte