malignant haemopoiesis

Question 1

what is it?

Answer 1

Characterised by increased numbers of abnormal and dysfunctional cells 
Loss of normal activity 
o	Haemopoiesis (e.g. acute leukaemias)
o	Immune function (e.g. certain lymphomas)

Question 2

what causes it?

Answer 2

increased proliferation
lack of differentiation
lack of maturation
lack of apoptosis

Question 3

what genetic factors lead to it?

Answer 3

genetic, epigenetic and environmental interaction
Acquired somatic mutations in regulatory genes (driver mutations vs passenger mutations)
o Multiple hits – more than single catastrophic event
Recurrent cytogenetic abnormalities – NOT causal in most but contributory

Question 4

what is the process of normal haemopoiesis?

Answer 4

polyclonal (malignant hameopoiesis is monoclonal)
o Driver mutations select ‘clones’ a population of cells from a single parent cell, parent cell has a genetic marker which is shared by the daughter cells
o Clones can diversify but have a similar genetic backbone
o Driver mutations confer growth advantage on the cells and are selected during the evolution of the cancer – passenger mutations don’t confer growth advantage but happened to be present in an ancestor of the cancer cell when it acquired a driver

Question 5

how are the types of malignancies classified

Answer 5

Based on lineage
o Myeloid
o Lymphoid
Based on developmental stage (precursor) within lineage
Based on anatomical site involved
o Blood involvement – leukaemia
o Lymph node involvement with lymphoid malignancy – lymphoma
Chronic lymphocytic leukaemia can involve blood and lymph nodes
Myeloma – plasma cell malignancy in marrow

Question 6

how so they present?

Answer 6

acute leukaemias & high-grade lymphomas are histologically and usually clinically more aggressive than chronic leukaemias & low-grade lymphomas
Features of histological aggression: large cells with high nuclear-cytoplasmic ratio, prominent nucleoli, rapid proliferation
Features of clinical aggression: rapid progression of symptoms