clinical oncology 5: leukaemia Flashcards
what is leukaemia?
cancer of the blood
- results from mutations in a single lymphoid / myeloid stem cell -> offspring exhibit abnormalities of proliferation / differentiation / survival -> uncontrollable reproduction of clone
epidemiology of leukaemia:
- 5% of all cancers
- most common cancer in young men/women
- kills more <35yo than any other cancer
how is leukaemia different to other cancers?
rarely a tumour - cancerous cells replace normal bone marrow cells & excess cells circulate in bloodstream
how is leukaemia classified?
chronic / acute (as supposed to benign / malignant respectively)
lymphoid / myeloid
what is the difference between lymphoid & myeloid leukaemia?
lymphoid: B/T cell lineage
myeloid: any other blood cell line
what mechanisms can give rise to leukaemia?
- mutation in known proto-oncogene
- creation of a novel gene eg a chimaeric / fusion gene
- dysregulation of a gene when translocation brings it under influence of promoter
- loss of function of tumour-suppressor gene
- increased chromosomal breaks
- DNA repair malfunctions
what are the identifiable causes of leukaemogenic mutations?
- irradiation
- anti-cancer drugs
- cigarette smoking
- chemicals eg benzene
what are the 4 types of leukaemia?
acute lymphoblastic (ALL) acute myeloid (AML) chronic lymphocytic (CLL) chronic myeloid leukaemia (CML)
what happens in AML?
cells proliferate but they do not mature -> myeloblasts build up in BM -> spread into blood -> failure to produce ‘end cells’
what do the mutations for CML usually affect?
- signalling protein in a pathway between cell surface receptor and nucleus
- internal cell kinetics & dynamics not as seriously affected in CML
- cells just become independent of external signals, interact with strom & apoptosis is inhibited
what happens in ALL?
increase in very immature cells (lymphoblasts) and failure to develop functional B&T cells
what happens in CLL?
lymphocytes are mature but abnormal
how does leukaemia cause disease?
accumulation of abnormal cells causes:
- leukocytosis
- hepatomegaly
- splenomegaly
- skin infiltration
- bone pain
- lymphadenopathy
- thymic enlargment
what blood characteristics does leukaemia cause?
- anaemia
- neutropenia
- thrombocytopenia
what are the metabolic effects of leukaemic cell proliferation?
- hyperuricaemia
- renal failure
- weight loss
- mild fever
- sweating
