Cancer 14: Leukemia as a disease Flashcards
What is leukaemia?
cancer of the blood
- they are the main cause of cancer death in people aged 1-34 years
- blood cancers are the most common cancers in men and women aged 15-24
Why does leukaemia occur?
it results from a series of mutations in a single lymphoid or myeloid stem cell
-these mutations lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukemic clone
What doe myeloid stem cells differentiate into?
- erythroblast
- megakaryoblast
- myeloblast
- monoblast
What do lymphoid stem cells differentiate into?
- pre B lymphocyte
- pro T lymphocyte
How many mutations are usually needed for leukaemia to become aggressive?
2
How is leukaemia different from other cancers?
- uncommon for patients to have tumours
- they have leukemic cells replacing normal bone marrow cells and circulating freely in the blood stream
- haemopoietic stem cells and normal lymphoid stem cells circulate between the tissues and the blood so the concepts of invasion and metastasis cannot be applied
- leukaemia’s that behave in a benign manner are called CHRONIC
- leukaemia’s that behave in a malignant manner are called ACUTE
How is leukaemia classified? (4)
- acute lymphoblastic leukaemia (ALL)
- acute myeloid leukaemia (AML)
- chronic lymphocytic leukaemia (CLL)
- chronic myeloid leukaemia (CML)
What important leukaemogenic mutations have been recognised in the development of leukaemia?
- mutation in a known proto-oncogene
- creation of a novel gene e.g. a chimeric or fusion gene
- dysregulation of a gene when translocation has occurred
What other reasons can cancer occur?
- loss of function of a tumour suppressor gene
- tendency to increased chromosomal breaks
- if the cell cannot repair DNA normally
What inherited ways can people get leukaemia?
- down’s syndrome
- chromosomal fragility syndrome
- defect in DNA repair
- inherited defects of tumour suppressor genes
What causes leukaemogenic mutations?
- irradiation
- anti-cancer drugs
- cigarette smoking
- chemicals e.g. benzene
What is AML?
-cells continue to proliferate but do not mature so there is a build up of myeloblasts in the bone marrow that spread into the blood. There is also failure of normal end cells e.g. neutrophils, monocytes, erythrocytes, platelets
What is CML?
the mutations usually affect a gene encoding protein in the signalling pathway between the cell surface receptor and the nucleus
-the protein is either a membrane receptor or a cytoplasmic protein
What are the main differences between CML and AML?
- the cell kinetics and function are not as seriously affected as in AML
- AML has failure of end cell production but CML has increased production of end cells
What does ALL cause?
-increase in very immature lymphoblasts with a failure of these to develop into mature T and B cells
