Concepts of Malignancy Flashcards
(31 cards)
How can we identify normal, more mature non-lymphoid cells?
morphology
How can we identify normal progenitors/stem cells? (3)
Cell surface antigens (immunophenotyping)= eg CD34
Cell culture assays
Animal models (not very practical)
Malignant haemopoiesis characterised by= (4)
increased numbers of abnormal & dysfunctional cells
loss of normal activity
- haemopoiesis (e.g. acute leukaemias/marrow-based malignancies)
- immune function (e.g. certain lymphomas)
Malignant haemopoiesis due to (3)
Increased proliferation (in the absence of a stimulus)
Lack of differentiation/maturation
Lack of apoptosis
Acute leukaemia (2)
Proliferation of abnormal progenitors with block in differentiation/maturation
(e.g. Acute Myeloid Leukaemia)
Chronic myeloproliferative disorders/neoplasm (MPN) (2)
Proliferation of abnormal progenitors, but NO differentiation/maturation block
(e.g. Chronic Myeloid Leukaemia)
What causes haematological malignancies? (4)
genetic, epigenetic, environmental interaction
ACQUIRED somatic mutations in regulatory genes
[driver mutations vs passenger mutations]
more than single catastrophic event
deletions, chromosomal translocations etc
‘Clone’ ?
population of cells derived from a single parent cell
Driver mutations can select ‘clones’ (2)
This parent cell has a genetic marker (driver mutation or chromosomal change) that is shared by the daughter cells
Clones can diversify but contain a similar genetic ‘backbone’
Normal haemopoiesis
polyclonal
Malignant haemopoiesis
monoclonal
Driver mutations
confer growth advantage on the cells and are selected during the evolution of the cancer
Passenger mutations
do not confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers
Lymphoid- cells (4)
Dendritic cells, B cells, T cells, NK cells
Myeloid- cells (5)
Dendritic cells, Erythrocytes, Platelets, Granulocytes, Macrophages
Haemopoietic stem cell= Lymphoid progenitor (lymphoma)
= T + B lymphocyte= Plasma cell
Haemopoietic stem cell= Myeloid progenitor (leukAemia)
= Red cells, Neutrophils, Platelets
Classifying cancers of the haemopoietic and lymphoid systems (4)
Site
Lineage
Stage of development/histology
Preservation of differentiation/maturation
acute leukaemias & high-grade lymphomas
histologically and clinically more aggressive than chronic leukaemias & low-grade lymphomas
Features of histological aggression: (3)
large cells with high nuclear-cytoplasmic ratio
prominent nucleoli
rapid proliferation
Features of clinical aggression:
rapid progression of symptoms
Acute leukaemias present =
(more commonly than chronic leukaemias)
with failure of normal blood cell production
Acute lymphoblastic leukaemia:
blood/marrow involving primitive, lymphoid malignancy
Acute myeloid leukaemia:
blood/marrow involving, primitive, myeloid malignancy