Leukaemia Flashcards
Leukaemia
- cancer of the blood
- first case recognised had raised wcc making blood appear whiter
- actually a bone marrow disease and not all patients have abnormal blood cells
- results from series of mutations in a single lymphoid or myeloid stem cell->leads progeny of cells to show abnormalities in proliferation, differentiation or cell survival->steady expansion of leukaemic clone
Epidemiology of blood cancer
- 5% of all cancers are cancers of the blood
- ~60 people per day diagnosed with cancer of the blood in the UK
- blood cancers=most common caners in men and women aged 15-24
- blood cancers=main cause of cancer death in people aged 1-34
- 1 in 45 of UK population will die of leukaemia, lymphoma or myeloma (blood cancers)
Cells involved in leukaemia
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Leukaemia differences from other cancers
1) most cancers exist as solid tumours but it is uncommon for leukaemia patients to have tumours->more often have leukaemic cells replacing normal bone marrow cells and circulating freely in bloodstream
2) haemopoietic and lymphoid cells behave differently from other body cells
Leukaemia classification
1) acute or chronic
2) lymphoid or myeloid (cell of origin)
- lymphoid can be B or T lineage
- myeloid can be any combination of granulocytic, monocytic, erythroid or megakaryocytic
Leukaemia classes
- Acute lymphoblastic leukaemia (ALL)
- Acute myeloid leukaemia (AML)
- Chronic lymphocytic leukaemia (CLL)
- Chronic myeloid leukaemia (CML)
Leukaemia pathogenesis
- results from series of mutations in a single stem cell=some mutations result from oncogenic influences, others are random errors (chance events) that occur throughout life and accumulate over time in individual cells
- loss of tumour-suppressor gene function can contribute to leukamogenesis (results from deletion or gene mutation)
- tendency to increase chromosomal breaks will result in increased leukaemia likelihood
- if cell cannot repair DNA normally=error persists (normal healthy person would have defect repaired)
Differences between acute (AML) and chronic (CML) myeloid leukaemia
AML:
- cells continue to proliferate but no longer mature so there is a build up of most immature cells (myeloblasts or blast cells) in bone marrow with spread into blood and a failure of normal functioning end cell production (neutrophils, monocytes, erythrocytes, platelets etc)
- responsible mutations typically affect transcription factors (multiple gene transcription affected)
- often oncogene product prevents normal function of protein encoded by its normal homologue
- CELL BEHAVIOUR=DISTURBED
CML:
- responsible mutations typically affect gene encoding protein (membrane receptor or cytoplasmic protein) in signalling pathway between cell surface receptor and nucleus
- cell kinetics and function not as seriously affected as in AML
- however, cell becomes independent of external signals, there are alterations in interaction with stroma, apoptosis is reduced (longer cell survival) and leukaemic clones expand progressively
AML=failure of end cell production
CML=increased end cell production
Differences between acute (ALL) and chronic lymphoid leukaemia (CLL)
ALL
-increase in lymphoblasts (very immature cells) with a failure of these to develop into mature T and B cells
CLL
-leukaemic cells are mature although abnormal (T cells or B cells)
Leukaemia disease characteristics
Accumulation of abnormal cells leads to:
- leucocytosis
- bone pain (acute if leukaemia)
- hepatomegaly
- splenomegaly
- lymphadenopathy (if lymphoid)
- thymic enlargement (if T lymphoid)
- skin infiltration
Metabolic effects of leukaemic cell proliferation:
- hyperuricaemia and renal failure
- weight loss
- low grade fever
- sweating
Crowding out of normal cells leads to:
- anaemia
- neutropenia
- thrombocytopenia
Acute lymphoblastic leukaemia (ALL) epidemiology
- largely a disease of children=highest incidence at 4 years old
- epidemiology suggests B-lineage ALL results from delayed exposure to a common pathogen, or that early exposure to a pathogen protects
- evidence relates family size, new towns, socio-economic class, early social interactions and variations between countries
- study suggested enterovirus infection gave protection against ALL
- epidemiology also suggests some leukaemias in infants/young children result from irradiation in utero, in utero exposure to certain chemicals (Baygon) and EBV infection
- rarely ALL results from mutagenic drug exposure
Acute lymphoblastic leukaemia clinical features
ABNORMAL CELL ACCUMULATION:
-bone pain
-hepatomegaly
-splenomegaly
-lymphadenopathy
-thymic enlargement
-testicular enlargement
CROWDING OUT OF NORMAL CELLS:
-anaemia causes fatigue, lethargy, pallor and breathlessness
-neutropenia causes fever and other features of infection
-thrombocytopenia causes bruising, petechiae and bleeding
Acute lymphoblastic leukaemia haematological features
- leucocytosis with lymphoblasts in the blood
- anaemia (normocytic, normochromic)
- neutropenia
- thrombocytopenia
- normal bone marrow cell replacement by lymphoblasts
Acute lymphoblastic leukaemia investigations
- full blood count and film
- liver and renal function tests
- uric acid
- bone marrow aspirate
- cytogenetic/molecular analysis
- chest x-ray
Immunophenotyping
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