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Leukaemia - Coggle Diagram

- - - - Fever
      - Malaise
      - Bleeding
      - Mouth ulcers
    - - e.g. nosebleeds
  - - - Symptoms of anaemia
        
        Pallor
        
        Lethargy
      - Symptoms of thrombocytopenia
        
        Purpura
        
        Spontaneous bruising
        
        Bleeding gums
    - - Bone pain
      - Lymphadenopathy in ALL
      - Moderate splenomegaly and hepatomegaly
        
        Especially in ALL
      - Infiltration of gums and skin in M\(_{4+5}\)
  - - - Increase in blasts
        
        75% marrow cells
        
        Normal is <5% marrow cells
    - - Impossible to distinguish types of blast
    - - Chloroacetate esterase
        
        Leukocyte isoenzymes of esterases 1,2,7 + 8
        
        Stained using substrate \(\alpha\)-naphthyl AS-D chloroacetate
        
        Differentiate granulocytic cell lines (CE positive) and monocytic cell lines (CE negative)
      - Peroxidase + Sudan black B
        
        Peroxidase activity
        
        Myeloperoxidase present in granulocyte + monocyte cell lines
        
        Sudan black B stains neutral fats, phospholipids + lipoprotein
        
        Reaction pattern = peroxidase reaction
        
        Distinguish between ALL and AML
      - Non-specific esterase
        
        No. of substrates for identification + localisation of esterases 3,4,5 + 6
        
        Differentiate between granulocytic + monocytic cell lines
        
        Monocytic = NSE positive
      - Acid phosphatase
        
        In lysosomes of haematopoietic cells
        
        Classification of lymphoproliferative disease
        
        In T-cell ALL
        
        Reaction localised to area of cytoplasm occupied by Golgi apparatus
  - - - DNApol activity present at high levels in lymphoid cells
      - Early marker for B + T-cell ALL
    - - Large increases in serum lysozyme in monocytic leukaemia
      - Smaller increases in myeloblastic leukaemia
- - - - Increased rate of proliferation
      - Reduced apptosis
      - Blocking of differentiation
      - Accumulation of blast cells in bone marrow which spills into blood
  - - - Repair results in abnormalities
        
        Deletion of entire chromosome or section
        
        Inversions of segment of chromosome
        
        Paracentric (does not include centromere)
        
        Pericentric (does include centromere)
        
        Translocation
        
        Most common
        
        Exchange of genetic material between chromosomes
        
        Fusion of PML-RARA genes from chromosomes 15 + 17 respectively
        
        Fused gene is an oncogene
- - - - RBCs
      - WBCs
      - Platelets
      - Anaemia
  - - - Replaced by abnormal cells
- - - - Incidence highest at 3-7yrs
    - - Based on morphology + cytochemistry
      - L1
        
        L2
        
        L3
        
        Burkitt-cell type
        
        Large blasts
        
        Moderate amount basophilic vacuolated cytoplasm
        
        Round to oval nucleus
        
        Stippled chromatin
        
        One or more distinct nucleoli
        
        Rare
        
        Fast-growing
        
        Too many B-cells form in blood + bone marrow
        
        Large, heterogenous
        
        Pleomorphic larger blasts
        
        Moderate amount of cytoplasm
        
        Irregular nuclei
        
        Fine chromatin
        
        One or more large distinct nucleoli
        
        Small, monomorphic
        
        Small round blasts
        
        Scant cytoplasm
        
        Round nucleus
        
        Homogenous chromatin
        
        Indistinct nucleolus
        
        Most common in children
        
        Best prognosis
  - - - FAB (French-American-British) classification system
        
        M\(_0\) - M\(_7\)
        
        M\(_0\)
        
        Undifferentiated
        
        M\(_1\)
        
        M\(_2\)
        
        M\(_3\)
        
        M\(_4\)
        
        2 more items...
        
        Acute promyelocytic leukaemia
        
        AML with granulocytic maturation
        
        AML without maturation
    - - Peroxidase positive
      - Large, crystalline cytoplasmic inclusion bodies
    - - Based on genetics
      - 1-7
  - - - Disease of the elderly
      - Rare in patients <40yrs
      - Male to female ratio
        
        2:1
    - - Anaemia is NOT an obvious symptom
        
        Especially in early stages
        
        10% cases develop haemolytic anaemia
      - Splenomegaly + hepatomegaly
      - Lymphadenopathy
      - Bruising + purpura
      - Infections
    - - 10% cases develop autoimmunity
      - Total WBC count
        
        15x10\(^9\)/L
        
        May be 300x10\(^9\) or higher
      - 70-99% cells are small mature lymphocytes
      - Smear cells common
        
        Fragile cells disrupted when making blood film
      - Immunological markers show mature cells to be B-cells in 90% cases
      - Rare T-CLL much more aggressive
      - Thrombocytopenia in later stages
      - Bone marrow is 30-50% infiltrated by lymphocytes
  - - - Chronic granulocytic leukaemia (CGL)
    - - Malignant proliferation of granulocytes in bone marrow + other haematopoietic organs
    - - Philadelphia (Ph) chromosome in haematopoietic cells
      - t(9;22)(q34;q11)
      - Ph chromosome is 22
        
        Where ABL-BCR (tyrosine kinase) fusion is
    - - 20% all leukaemia
      - 1 per 100,000 in population
      - 20-60yrs of age
    - - Anaemia
      - Bleeding
        
        Abnormal platelet function
      - Splenomegaly + hepatomegaly
      - Hypermetabolism
        
        Inc. BMR
        
        Fever
        
        Weight loss
        
        Night sweats
      - Bone pain
        
        Hypercellularity of marrow
      - Prolonged infections
    - - Normochromic/normocytic (NN) anaemia
      - WBC count
        
        Usually 50-300x10\(^9\)
        
        May be higher
      - Complete range of myeloid cells seen in peripheral blood
        
        Myelocytes
        
        Metamyelocytes
        
        Band forms
        
        Mature neutrophils
        
        Few myeloblasts + promyelocytes may be seen
      - Biochemical abnormalities
        
        Increased level of lactate dehydrogenase (LDH)
        
        Serum B12 - 15x normal level
        
        Inc. synthesis of transcobalmins I + III by leukaemic granules
      - Abnormally small chromosome
        
        From translocation of portion of q22 to ch9
        
        Diagnostic indicator of CML
- - - - Blood forming cells
      - Neoplasms originating from haematopoietic stem cells in the bone marrow
      - Widespread involvement in peripheral blood
    - - Immune cells e.g. B-/T-cels
      - Neoplasms arising from lymphocytes
- - - - Cell growth regardless of circumstances
    - - Chronic myelogenous leukaemia
      - Acute lymphoblastic leukaemia
      - Tyrosine kinase
    - - Transcription factor
      - Leukaemias
  - - - Ras inhibitor
        
        Myeloid leukaemia
- - - - Angiogenesis enhanced through stimulating factors