Leukaemia Flashcards
What is leukaemia
Cancer of the blood
Bone marrow disease
Describe the role of mutations in leukaemia
Series of mutations in a single lymphoid or myeloid stem cell
The cell’s progeny show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone
What distinguishes leukaemia from other cancers
Most cancers exist as a solid tumour
However, it is uncommon for leukaemia patients to have tumours
More often they have leukaemic cells replacing normal bone marrow cells and circulating freely in the blood stream
What do “acute” and “chronic” refer to when describing leukaemias
“benign” = chronic (disease occurs for a long time)
“malignant” = acute (disease is aggressive and patient dies rapidly if not treated)
What are the classifications of leukaemia
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
What are the important leukaemogenic mutations
Mutation in a known proto-oncogene
Creation of a novel gene, e.g. a chimaeric or fusion gene
Dysregulation of a gene when translocation brings it under the influence of the promoter or enhancer of another gene
What are the causes of leukaemia
Inherited abnormalities that contribute to leukaemogenesis (downs, defects in DNA repair, chromosomal fragility syndromes) Irradiation Anti-cancer drugs Smoking Chemicals e.g. benzene
Describe acute myeloid leukaemia
In AML, cells proliferate but they no longer mature, so the most immature cells (myeloblasts) build up in the BM and spread into the blood
There is then a failure to produce ‘end cells’ (normal, functioning neutrophils/erythrocytes/platelets etc.)
What are the mutations usually responsible for acute myeloid leukaemia
Usually affect transcription factors so that the transcription of multiple genes is affected
What are the mutations usually responsible for chronic myeloid leukaemia
usually affect a signalling protein in a pathway between a cell surface receptor and the nucleus (which could be the receptor)
What is the difference between acute and chronic myeloid leukaemia?
Internal cell kinetics and dynamics are not as seriously affected as AML
Cells just become independent of external signals, interact differently with stroma, and apoptosis is inhibited.
There is increased production of ‘end cells’
What is the difference between acute and chronic lymphoid leukaemias?
Acute lymphoblastic leukaemia has an increase in very immature cells (lymphoblasts) with a failure of these to develop into mature T and B cells
In chronic lymphoid leukaemias, the leukaemic cells are mature, although abnormal, T cells or B cells
How does leukaemia cause disease?
Accumulation of abnormal cells
Crowding out normal cells
What does accumulation of abnormal cells in leukaemia lead to
Leukocytosis Hepatomegaly Splenomegaly Skin infiltration Bone pain (if acute) Lymphadenopathy (if lymphoid) Thymic enlargement (if T lymphoid)
What does crowding out of normal cells in leukaemia lead to
Anaemia
Neutropenia
Thrombocytopenia
