Malignant haem Flashcards
how are normal mature cells identified
morphology
cell surface antigens (e.g. glycophorin A = red cells)
enzyme expression (e.g. myeloperoxidase = neutrophils)
how are proginators/stem cells identified
cell surface antigens - immunophenotyping e.g. CD34
cell culture assays
what happens in malignant haemopoiessi
increased numbers of dysfunctional cells and may have loss of the normal haemopoietic reserve
one or more of: increased prolif lack of differentiartion lack of maturation lack of apoptosis
what happens to the cells in acute leukemia
abnormal proliferation - large number of similar looking cells
lack of maturation
causes of haematological malignancies
genetic
enviro
somatic mutations in regulatory genes: driver V passenger mutations [noise]
multiple mutations or can be one single catastrophic event
recurrent cryogenic abnormalities -> contributory rather than the cause of the cancer
difference between passenger and driver mutations
driver - confer growth advantage, positively selected during the evolution of the cancer
passenger - do not confer growth advantage, happened to be present in an ancestor of the cancer cell when it acquired on of its driver
what is the concordant rate with twins in ALL
10-15%
how many people over the age of 65 for driver mutations that are associated with haematological malignancies
around 10%
how can the genetic defect be found in ALL
by investigating the guthrie card
normal haemopoiesis
malignant haemopoeisis
polyclonal
monoclonal
classification of haematological malig
acute/chronic presentation - depends on type and stage of defect
anatomical site: -medullary/extramedullary
-leukaemia (blood)/lymphoma
lineage:
- myeloid
- lymphoid
types of lymphomas
high grade - aggressive histology: large primitive cells and clinically aggressive
low grade - generally less aggressive
what is odd about chronic lymphocytic leukaemia
involves not just blood/bone marrow but lymph nodes
myeloma is what
plasma cell malignancy of the bone marrow
what are acute leukaemia
rapidly progressive clonal malignancy of the marrow/blood with maturation defects
excess of blasts >20% in either peripheral blood or bone marrow
decrease/loss of normal haemopoietic reserve
types of acute leukaemia
actual myeloid leu
acute lymphoblastic leu
what is ALL
malignant disease of lymphocytes
who is ALL common in
most common childhood cancer
presentation of ALL
marrow failure - anaemia, infection, bleeding
leukaemia effects - high ECC, nervous system effects, lymph nodes sometimes causing venous obstruction [SVC obstruction]
bone pain - v severe
acute myeloid leu more common in who
presentation
elderly >60
de novo or secondary
presentation similar to aLL -> doesn’t involve CNS
what other ways can some subgroups of AML present
DIC
Gum infiltration
investigations for acute leu
blood count and film - low hb, white cells may be high, low platelets, low neutrophils
film - Auer rods in acute myeloid leukaemia
coag screen
bone marrow aspirate
bone marrow aspirate
morphology - mononuclear, high nuclear: cytoplasmic ration, very metabolically active
immunophenotype if no auer rods can be seen - CD33 is seen on myeloid cells not lymphoid cells, CD34
cytogenetics - help w dx and prognostic significance
trephine (piece of bone) - better assessment of cells if aspirate sub optimal
why is immunophenotyping required or a definitive dx
cells from AML and ALL look alike
treatment for both are different
