leukaemia Flashcards
what is leukaemia *
cancer of the blood
means white blood - marked increase in white cell count
also a bone marrow disease - not all patients have abnormal cells in the blood - but abnormalities on bm spill into blood
describe the test Attach Soundstubes *
anticoagulated blood
centrifuged
plasma layer on top
white layer - buffy coat because off white - increasing white cell count
red layer - rbc
describe the genetics of leukaemia *
series of mutations in a single lymphoid/myeloid stem cell - or one that can give rise to both (pleuripoietic stem cells)
mutations in pleuripoietic stem cell = mixed phenotype acute leukaemia - with lymphoid and myeloid leukaemic cells
lymphoid stem cell = T B or NK leukaemias
myeloid = myeloid leukaemias
need >1 mutation - no abnormality is seen clinically with 1 mutation (can see molecularly), second mutation makes the clone more aggressive - expand at the expense of other polyclonal cells
the mutations = abnormalities in proliferation (too fast), differentiation (dont mature to end stage cells) or cell survival (live too long) = steady expansion of leukaemic clone
why is leukaemia different from different cancers
uncommon to have tumours
more often the leukaemic cells replace normal BM cells and then circulate in blood
normal haemopoietic and lymphoid stem cells circulate between tissues and the blood - therefore the concepts of invasion and metastasis dont really work because the cells normally enter surrounding tissue and spread through vessels
terminology used to describe leukaemias *
those that behave in a benign manner - called chronic - means disease goes on for a long time
those that behave in a malignant manner - acute - means if not treated the cancer is very aggressive and the patient will die in weeks or months
what is the difference between lymphoid and myeloid leukaemia *
lymphoid - B T NK lineage
myeloid - any combination or granulocytic, monocytic, erythroid or megakaryocytic or multiple lineages
what are the 4 classifications of leukaemia *
acute lymphoblastic leukaemia
acute myeloid leukaemia
chronic lymphocytic leukaemia
chronic myeloid leukaemia
why do people get leukaemia *
series of mutations in a single stem cell
some mutations are from identifyable, or unidentifyable oncogenic influences - environmental
others are chance events that happen through life and accumulate in individual cells
what are the important leukaemogenic mutations *
in proto-onchogene
creation of novel gene - chimaeric or fusion gene - translocation between chromosomes - have 5’ part of 1 gene and 3’ part of another
dysregulation of a gene when translocation brings it under the influence of promoter or enhancer of another gene - turned on innappropriately
loss of function of tumour suppressor gene - from deletion or mutation - leukaemia becomes more acute
genetic tendancy to increased chromosomal breaks - likelyhood of leukaemia is increased
if cell cant repair DNA normally - error might persist but in a normal person this would be repaired - this is an inherited condition
down’s syndrome can contribute
causes of leukaemogenic mutations *
irradiation
anti-cancer drugs - cause mutations
cigarette smoking
chemicals - benzene
where are the mutations in leukaemia *
somatic cells
mutations in germ might bring favourable, neutral or unfavourable characteristics to the species
somatic may be beneficial, neutral or harmful - harmful eg leukaemia
beneficial when a mutation leads to return to normal phenotype in a cell with an inherited abnormality eg an immune deficiency or bm failure system
describe acute ML *
cells continue to proliferate but dont mature
there is a build up of immature blast cells - myeloblasts or blast cells in bm with spread into the blood
there is a failure of production of normal functionining end cells - neutrophils, monocytes and erythrocytes, platelets because bm is been taken over by immature cells
also platelets are used up in DIC which is associated with 1 type of AML
genetics of AML *
mutations affect TF - so transcription of mutiple genes is affected
the product of an onchogene prevents the normal function of the protein coded by its normal homologue
cell behaviour disturbed
describe CML *
mutations affect a gene encoding a protein signalling pathway between a cell surface receptor and the nucleus
protein encoded may be a membrane receptor or cytoplasmic protein - therefore effect of cell behaviour not as profound
but mutation may activate the cell - cell becomes independant of external signals, alterations in reactiosn with the stroma and there is reduced apoptosis so that the cells survive longer and leukaemic clone expands progressively
there is increased production of end cells
what is the difference between acute and chronic lymphoid leukaemia *
acute lymphoplastic leukaemia - increase in 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, B and NK cells
chest x-ray of infiltrated thymus
describe blood fim for someone with ALL *
lymphoblasts - large compared to lymphocytes
high nucleocytoplasmic ratio
chromatin not dense in cells - delicate condensation
no platelets
describe a normal bone marrow film *
cells normal and a mix of types
red arrow - myeloblasts
green arrow - promyelocyte - granules
myelocyte
band neutrophil
segmented neutrophil
nucleated red cell
lymphocyte
