essay 27 - leukemias - etiology, pathogenesis, types

what are leukemias

• malignant disorders of the blood and bone marrow, characterised by uncontrolled proliferation of immature or abnormal white blood cells

risk factors for leukemia

1. genetic factors = chromosomal abnormalities (e.g philadelphia chromsosome in chronic myeloid leukemia - CML). inherited syndromes (e.g down syndrome increases leukemia risk)

2. radiation exposure = high dose ionising radiation (atomic bombe survivors, radiation therapy)

3. chemical exposure = benzene exposure. chemotherapy drugs (alkylating agents) increase secondary leukaemia risk

4. viral infections = human T-lymphotrophic virus type I (HTLV-I) is linked to adult T-cell leukemia

5. bone marrow disorders = myelodysplastic syndromes can evolve into leukemia

6. immune system dysfunction = some immunodeficiencies predispose to leukemia

pathogenesis of leukemia involves genetic mutations that affect normal blood cell production:

1. genetic mutation= mutation occurs in a single hematopoietic stem cell or progenitor cell in the bone marrow

2. clonal expansion = the mutated cell has uncontrolled clonal proliferation. cells fail to mature properly leading to accumulation of immature blasts

3. suppression of normal haematopoiesis = malignant cells crowd out normal bone marrow cells. leads to:
   - anaemia (decrease RBC → fatigue, pallor)
   - thrombocytopenia (decrease platelets → bleeding, bruising)
   - leukopenia or dysfunctional leukocytes (decrease functional WBCs → infections)

4. tissue infiltration = leukemic cells can infiltrate other organs = lymph nodes. liver. spleen. CNS

describe acute lymphocytic leukemia (ALL)

• malignant cell = immature lymphoid precursor cells (mostly pre-B lymphoblasts)

• primary age group = children (peak incidence between 2-5 years old). can also occur in adults (weak prognosis)

• key characteristics:
  - rapid onset
  - bone marrow packed with lymphocytes
  - CNS involvement is common (headache, vomiting, cranial nerve palsies)
  - good prognosis in children (better survival rates with treatment)

describe acute myelocytic leukemia (AML)

• malignant cell = granulocytic stem cells

• primary age group = adults, especially older adults (>60 years). rare in children

• key characteristics:
  - rapid progression
  - bone marrow and blood full of myeloblasts
  - presence of Auer rode (needle-like inclusions) in cytoplasm of blasts
  - reacquires aggressive chemotherapy; prognosis variable

describe chronic lymphocytic leukemia (CLL)

• malignant cell = mature but dysfunctional B-lymphocytes

• primary age group = older adults (usually >60 years)

• key characteristics:
  - slow progression (“chronic”)
  - often found incidentally on routine blood tests (elevated lymphocyte count)
  - symptoms = fatigue, enlarged lymph nodes (lymphadenopathy), splenomegaly
  - immune dysfunction= increased risk of infection
  - characteristic findings= “smudge cells” (fragile lymphocytes that break during side preparation)

Describe chronic myelocytic leukemia (CML)

• malignant cell = granulocytic stem cells

• primary age group = adults, typically aged 30-60 years

• key characteristics:
  - slow, gradual progression
  - extremely high white blood cell count
  - associated with philadelphia chromosome (t(9;22) → BCR-ABL fusion gene)
  - symptoms = splenomegaly, fatigue, wight loss, early satiety
  - may transforms into a rapidly fatal acute leukemia phase (“blast crisis”)

describe acute monocytic leukemia

• malignant cell = immature monocyte (monoblasts)

• primary age = young adults and middle aged adults

• key characteristics:
  - subtype of AML (specifically M5 subtype in FAB classification)
  - prominent gum infiltration (gingival hypertrophy)
  - skin infiltrates (“leukemia cutis”) may be seen
  - high white blood cell counts with monocytosis
  - rapid progression if untreated

describe hairy cell leukemia

• malignant cell = mature b-lymphocytes with abnormal “hairy” projections on the surface

• primary age group = middle aged to older adults, predominately males

• key caharcteristics:
  - rare, indolent (slow-growing) leukemia
  - massive splenomegaly (enlarged spleen)
  pancytopenia (decrease RBCs, decreased WBCs, decrease platelets)
  - bone marrow is often fibrotic (“dry tap” on aspiration)
  - staining for tartrate-resistant acid phosphatase (TRAP positive) is characteristics