Introduction to Leukaemia Flashcards
What is leukaemia
Malignant disorders of haematopoietic stem cells characteristically associated with an increased number of white cells in bone marrow or/and peripheral blood
What are haematopoetic stem cells
Multipotent- can give rise to cells of every blood lineage
Self maintaining- a stem cell can divide to produce more stem cells
What are progenitor cells
Can divide to produce many mature cells
But cannot divide indefinitely
Eventually differentiate and mature
What is the difference between undifferentiated and committed progenitor cells
Undifferentiated (multipotent): you cannot tell the difference between them morphologically because they do not show the characteristics of mature cells
Committed (unipotent): already committed as to what they will become when they generate mature cells
How does leukaemia arise
It is a clonal disease- all the malignant cells derive from a single mutant stem cell
It form sit sown progenitor cells
What is the incidence of leukaemia
The higher incidence rate in the elderly, increases with ageing
Childhood cases are rising now at 31%
what are the initial symptoms of leukaemia
Typically first presents with symptoms due to loss of normal blood cell production:
- Abnormal bruising-commonest
- Repeating abnormal infection
- Sometimes anaemia
How can we clinically diagnose leukaemia and what does each test show
- Peripheral blood blasts test (PB): to check for presence of blasts and cytopenia. >30% blasts are suspected of acute leukaemia.
- Bone marrow test/biopsy (BM): taken from pelvic bone and results compared with PB.
- Lumbar puncture: to determine if the leukemia has spread to the cerebral spinal fluid (CSF).
How can we diagnose leukaemia pathologically
- Cytomorphology
- Immunophenotyping
- Next-generation sequencing
- Flow cytometry
- Fluorescence in situ hybridation (FISH)
What are the predisposing factors for leukaemia
- Genetic risk factors
- Lifestyle-related
- Uncertain, unproven or controversial factors
- Environmental risk factors
How can genetic risk factors cause disease
NOT usually hereditary
(except for some cases of Chronic Lymphocytic Leukaemia (CLL))
Some rare genetic diseases may predispose to leukaemia, e.g. Fanconi’s anaemia, Down’s syndrome
what genetic risk factors that cause leukaemia
- Gene mutations involving oncogenes (activation) or/and tumour suppressors (inactivation).
- Chromosome aberrations:
Translocations (e.g. BCR-ABL in CML).
Numerical disorders (e.g. trisomy 21-Down syndrome). - Inherited immune system problems (e.g. Ataxia-telangiectasia, Wiskott-Aldrich syndrome).
what environmental risk factors that cause leukaemia
Radiation exposure:
- acute radiation accidents
- atomic bomb survivors
Exposure to chemicals and chemotherapy:
- Cancer chemotherapy with alkylating agents (e.g. Busulphan)
- Industrial exposure to benzene
Immune system suppression:
- e.g. After organ transplant
what lifestyle-related risk factors that cause leukaemia
- Smoking
- Drinking
- Excessive exposure to sun
- Overweight
what controversial risk factors that cause leukaemia
- Exposure to electromagnetic fields
- Infections early in life
- Mother’s age when the child is born
- Nuclear power stations
- Parent’s smoking history
- Foetal exposure to hormones