Leukaemia Flashcards
(42 cards)
What is the most common cancer in the 15-24 age group?
Cancers of the blood
What is the literal meaning of leukaemia?
White blood
Where does the problem exist in leukaemia?
Bone marrow (not all patients have abnormal cells in the blood)
What does leukaemia result from? What are the consequences to the progeny of the mutated cell?
A series of mutations in a single lymphoid or myeloid stem cell
Progeny show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone
Which cells can be affected in leukaemia?
Pluripotent haematopoietic stem cell Myeloid stem cell Lymphoid stem cell Pre B lymphocyte Pro T lymphocyte
What are the equivalent terms for ‘benign’ and ‘malignant’ in terms of leukaemia?
Benign= CHRONIC Malignant= ACUTE– very aggressive
What are the four main types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia
Explain the significance of the terms acute lymphoblastic leukaemia and chronic lymphocytic leukaemia.
ALL: cells are immature (lymphoblasts)- fail to develop into mature T or B cells
CLL: cells are abnormal mature lymphocytes
What are the important leukaemogenic mutations that have been recognised?
Mutation in a known proto-oncogene
Creation of a novel gene e.g. chimeric or fusion gene
Dysregulation of a gene when translocation brings it under the influence of a promoter or enhancer of another gene
State 4 inherited or other constitutional abnormalities that can contribute to leukaemogenesis.
Down syndrome
Chromosomal fragility syndromes/ tendency to increased chromosomal breaks
Defects in DNA repair mechanisms
Inherited defects in tumour suppressor genes
State 4 identifiable causes of leukaemogenic mutations
Irradiation
Anti-cancer drug
Cigarette smoking
Chemicals e.g. benzene
What type of cell is seen in abundance in acute myeloid leukaemia?
Immature myeloid cells: cells continue to proliferate but no longer mature so there is a build up of immature cells (myeloblasts) in the bone marrow, which spread to the blood
Explain how acute myeloid leukaemia leads to bone marrow failure.
Leukaemic cells crowd out normal cells in bone marrow leading to a decrease in the production of normal functioning end cells e.g. neutrophils, monocytes, platelets
What do the responsible mutations normally affect in AML?
Transcription factors: transcription of multiple genes is affected
Often the product of an oncogene prevents normal function of the protein encoded by its normal homologue
Leads to changes in cell kinetics + cell functions
What do the responsible mutations normally affect in CML?
A gene encoding a protein in the signalling pathway between a cell surface receptor + the nucleus
The protein encoded may be a membrane receptor or a cytoplasmic protein
Describe the nature of the leukaemic cells in CML.
Mature lymphocytes (cell kinetics + function are not as seriously affected as in AML) but cells become independent of external signals, there are alterations in the interaction with stroma + there is reduced apoptosis so cells survive longer + the leukaemic clone expands progressively
How is the production of end cells affected in AML and CML?
AML: Failure in production of end cells
CML: increase in production of end cells
What are 5 metabolic effects of leukaemic cell proliferation?
Hyperuricaemia Renal failure Weight loss Low grade fever Sweating
Which type of leukaemia increases the risk of intraventricular haemorrhage and why?
Acute promyelocytic leukaemia (APML): associated with DIC so platelet count + fibrinogen are low leading to increased risk of fatal haemorrhage
How can leukaemia cause proliferation of the gums?
Infiltration of leukaemic cells + monocytes can lead to inflammation of the gums
Small haemorrhages due to thrombocytopenia
What does epidemiology suggest that B lineage acute lymphoblastic leukaemia may result from?
Delayed exposure to a common pathogen or that early exposure to pathogens protect
What 4 factors that relate to risk of leukaemia?
Family size
New towns
Socio-economic class
Early social interactions
What can leukaemias in infants and young children result from?
Irradiation in utero
In utero exposure to certain chemicals
What are 6 clinical features of acute lymphoblastic leukaemia? What do they result from?
Bone pain Hepatomegaly Splenomegaly Lymphadenopathy Thymic enlargement Testicular enlargement All result from the accumulation of abnormal cells
