Cancer as a Disease: Leukaemia Flashcards
What is leukaemia a result of?
a series of mutations in a single lymphoid or myeloid stem cell
- Pluripotent hematopoietic stem cell
- Myeloid/lymphoid stem cell.oPro-/Pre-T/B lymphocyte
How is leukaemia classified?
Acute or chronic
- Lymphoid or myeloid origin
> Lymphoid can be B or T lineage
> Myeloid can be any combination of granulocytic, monocytic, erythroid or megakaryocytic
- Benign leukaemia = chronic
Malignant = acute (aggressive and quick death if untreated)
What are the final classes of leukaemia?
- ALL – Acute Lymphoblastic Leukaemia
- AML – Acute Myeloid Leukaemia
- CLL – Chronic Lymphocytic Leukaemia
- CML – Chronic Myeloid Leukaemia
What are leukaemogenic influences?
- Proto-oncogene mutations
- Novel gene creation – e.g. a chimeric or fusion gene
- Dysregulation of a gene – when translocation brings the gene under the influence of a promotor or enhancer of another gene
- TSG loss of function – deletion or mutation of both copies
What are some inherited causes of leukaemogenesis?
- Down’s syndrome
- Chromosomal fragility syndromes
- Defects in DNA repair
- Inherited defects of TSGs
What are some identifiable causes of mutations?
- irradiation
- anti-cancer drugs
- cigarette smoking
- chemicals e.g benzene
What happens in AML?
Cell continue to proliferate but they do not mature, leading to:
- Build-up of immature cells
- Failure of production of normal functioning end cells such as neutrophils, monocytes, platelets, etc
- Responsible mutations usually affect transcription factors
- Often is due to the product of an oncogene affecting proteins
- failure of production of end cells
What happens in CML?
- Responsible mutations usually affect genes encoding proteins (membrane receptor or cytoplasmic proteins) involved in the signalling pathways from receptors
- Cell kinetics & function are not as seriously affected as in AML - But there is still reduced apoptosis and the cell progressively expands in population
- increased production of end cells
What are the differences between ALL and CLL?
Acute lymphoblastic leukaemia (ALL):
- Increase in very immature cells (lymphoblasts) with a failure of these to develop to mature B/T cells
Chronic lymphoid leukaemia (CLL):
- Leukaemic cells are mature but abnormal.
What are the characteristics of leukaemia?
Caused by an accumulation of abnormal cells leading to:
- Leucocytosis
- bone pain (acute)
- hepatomegaly
- splenomegaly
- lymphadenopathy (if lymphoid)
- thymus enlargement (if T lymphoid)
- skin infiltration
Metabolic effects of Leukaemic cell proliferation:
- Hyperuricemia and renal failure
- weight loss
- low-grade pyrexia
- hidrosis
Crowding out of normal cells leads to:
- anaemia
- neutropenia
- thrombocytopenia
- There is a loss of normal immune function (in CLL)
What group is mainly affected by ALL?
largely disease of children - highest incidence at age 4
What may some leukaemias in children be a result of?
- Irradiation in utero
- In utero exposure to certain chemicals – Baygon, Dipyrone
- EBV
- Rarely – exposure to a mutagenic drug
What are the clinical features of ALL?
abnormal cell accumulation:
- Bone pain
- Hepatomegaly and splenomegaly
- Lymphadenopathy
- Thymic enlargement
- Testicular enlargement
crowding out of normal cells:
- Anaemia – fatigue, lethargy, pallor, dyspnoea
- Neutropenia – fever and features of infection
- Thrombocytopenia – bruising, petechiae, bleeding
What are the haematological features of ALL?
- Leucocytosis with lymphoblasts in the blood
- Anaemia (normocytic, normochromic)
- Neutropenia
- Thrombocytopenia
- Lymphoblasts replacing normal bone marrow cells
What investigations are done for ALL?
- FBC with liver and renal function tests
- Bone marrow aspirate
- Cytogenic/molecular analysis
- Chest x-ray.
