introduction to Leukaemia Flashcards
define leukaemia
malignant disorders of haematopoietic stem cells associated with increased number of WBC in bone marorw/peripheral blood
what are haematopoietic stem cells
multipotent
self maintaining = stem cells can divide to produce more stem cells
can give risk to progenitor cells
describe progenitor cells
divide to form mature cells, cannot divide inherently, eventually differentiate and mature
describe 2 types of progenitor cells
- undifferentiated progenitor cells = cant tell difference between them morphologically as they dont show characteristics of mature cells
- committed progenitor cells = unipotent, committed as to what they’d become and when they generate mature cells
describe incidence of leukaemia
related to age, higher in older people
4/10 new cases per year 75+
higher in males
describe presentation of leukaemia
abnormal bruising
repeating abnormal infection
sometimes anaemia
diagnosis of leukaemia
extract biopsy from bone marrow, from pelvic bone, compared with PB
peripheral blood blast test = check for presence of blasts and cytopenia
lumbar puncture = determines if leukaemia has spread to cerebral spinal fluid
describe other diagnosis methods
cytomorphology immunophenotyping next gen sequencing flow cytometery fluorescence insitu hybridisation
aetiology of leukaemia
exact cause unclear
combo of predisposing factors = lifestyle/genetic risk
describe genetic risk factors
not usually hereditary
gene mutations involving oncogenes or activation of tumour suppressors
chromosome abberrations e.g. translocations
inherited immune system problems
environmental risk factors
radiation exposure
exposure to chemicals and chemotherapy
immune system suppression
lifestyle related risk factors
smoking/drinking exposure to electromagnetic fields infections early in life mothers age when child is born nuclear power station
difference between lymphoid vs myeloid leukaemia
acute and chronic
describe acute disease
rapid onset and short but severe cause
acute leukaemia
- undifferentiated
- uncontrolled clonal and accumulation of immature WBC
describe chronic disease
persisting over a long time
differentiated
uncontrolled clonal and accumulation of mature WBC
type of acute leukaemia
acute lymphoblastic and myeloblastic
type of chronic leukaemia
chronic lymphocytic and granulocytic
acute leukaemia in depth
characterised by large number of lymphoblasts or myeloidblasts in bone marrow = undifferentiated
symptoms:
thrombocytopenia = bruising, nosebleed, bleeding from gums
neutropenia = recurrent infections/fever
anaemia
describe acute lymphoblastic leukaemia
commonest cancer of childhood cancer of immature lymphocytes b cell and t cell leukaemia treatment = chemotherapy 1/10 patients relapse
describe acute myeloblastic leukaemia
70 children under 16 diagnose per year
cancer of immature myeloid WBC
based of FBA system
chemotherapy, monoclonal antibodies, allogeneic bone marrow transplant therapy
results in 5 year event-free survival of 50-60%
chronic leukaemia in depth
increased no. of differentiated cells
originates from large number of mature lymphocytes in bone marrow and peripheral blood
symptoms = recurrent infections, anaemia, thrombocytopenia, lymph node enlargement
chemotherapy treatment
describe chronic myeloid leukaemia
large number of mature myeloid wbc
asymptomatic and discovered via routine blood tests
diagnosis = high WBC count in blood and bone marrow, philadelphia chromosome present
imatinin therapy treatment
describe BCR-ABL oncogene
95% of cases of cml = have detectable philadelphia chromsome
balanced translocation of t(9;22) and q(32;q11) = causes philadelphia chromosome
BCR = encodes protein that needs to be constantly active
ABL = encodes protein tyrosine kinase whose activity is tightly regulated
BCR-ABL. = constitutive protein tyrosine kinase activity
unregulated BCR-ABL causes
proliferation of progenitor cells in absence of growth factors
decreased apoptosis
decreased adhesion to bone marrow stroma
95% of CML cases have phi chromosome
