Cancer 14 - Leukaemia Flashcards
Describe leukaemia
Leukaemia (WBC) is a cancer of blood
Bone marrow disease, not all patients have abnormal cells in blood
Leukaemia - occurs as a result from mutations in single lymphoid or myeloid stem cells —> causing steady expansion of leukaemic clone
Usually 2 mutations involved - 1st mutation = growth advantage. 2nd mutation = more aggressive –> sub clone expands, causing leukaemic clone expansion. May be years between first and second mutation
It is uncommon for leukaemia to be solid tumours. Expand
It is more often that leukaemic cells replace normal bone marrow cells and circulate freely in blood
Describe the classification of leukaemias
Benign behaviour = chronic
Malignant behaviour = acute
Depends on cell of origin - Myeloid or Lymphoid?
Myeloid if B/T cell origin
Lymphoid if any combo of granulocytic, monocytes, erythroid or megakaryocytic anaemia
i. e.
1. Acute Lymphoblastic Leukaemia (ALL)
2. Acute Myeloid Leukaemia (AML)
3. Chronic Lymphocytic leukaemia (CLL)
4. Chronic myeloid leukaemia (CML)
Describe the development and causes of leukaemia
Cause = mutations in single stem cell
Important leukaemogenic mutations:
- Mutation in known proto-oncogene
- Creation of novel gene e.g. chimeric/fusion gene
- Dysregulation of gene - when translocation brings it under influence of promotor/enhancer of another gene
Other contributors include: Loss of TSG function, increased tendency for chromosomal breaks, if incorrect DNA repair
What are some inherited abnormalities that may contribute to leukaemogenesis?
- Downs syndrome
- Chromosomal fragility syndromes
- Defects in DNA repair
- Inherited defects of TSGs
What are identifiable causes of leukaemogenic mutations?
- Irradiation
- Anti-cancer Drugs –> DNA
- Cigarette smoke
- Chemicals - benzene
Highlight the differences between AML and CML
In AML:
- IMMATURE cells proliferate
- immature cells (myeloblasts) develop in bone marrow —> fail to make normal cells in bone marrow
- mutations typically affect transcription factors
- cell behaviour profoundly disturbed
In CML:
- mutations affect gene involved in signalling pathway between receptor and nucleus (affected protein may be surface membrane receptor or cytoplasmic protein)
- cell kinetics/function not as seriously affected as in AML
- Cell becomes independent of external signals —> reduced apoptosis (and altered interaction w stroma)–> cells survive longer —> leukaemic clones expand progressively
- CML = increased production of other blood cells (but in AML, fail to produce other blood cells)
What is the difference between ALL and CLL
ALL: increase in immature cells (lymphoblasts) –> failure to develop into mature T/B cells
CLL: leukaemic cells are mature, abnormal T/B/NK cells
What can the accumulation of abnormal cells (as seen in leukaemia) lead to
- Leukocytosis - bone pain (if Acute leukaemia)
- Hepatomegaly and splenomegaly
- Lymphadenopathy (if lymphoid)
- Thymic enlargement (if T lymphoid)
- Skin infiltration and tumour formation and haemorrhage
What are the metabolic effects of leukaemic cell proliferation
- Hyperuricaemia (increased DNA breakdown in cells)
- Renal failure (excess urea depositing in kidneys in acute leukaemia)
- Weight loss
- Low grade fever and sweating
What can the crowding out of normal cells in leukaemia lead to (common in acute leukaemia)
- Anaemia
- Neutropenia
- Thrombocytopenia —> greater haemorrhage risk (also due to DIC)
Name 2 abnormalities that occur in AML
Haemorrhage and infiltration of leukaemic cells into gums
Why does CLL make one more infection prone
Loss of normal immune function due to loss of normal T and B cells
Describe the epidemiology of ALL
Children mainly (2-5) Mutation 1 usually in utero, 2nd after birth
Small peak in ALL 50+ (but different genetic abnormalities in adults and children with ALL)
B-lineage ALL may result from delayed exposure to common pathogen
Y. Early exposure to pathogens protects from B-lineage ALL
