Flashcards in Concepts in Malignant Haematology and Acute Leukaemia Deck (97)
** on every card with exam knowledge **
Name the 5 processes which are important in the normal kinetics of haempoiesis.
* Differentiation or lineage commitment.
** What techniques/methods can be used to identify normal (more mature) cells? **
** Morphology ** - blood count and film
Cell surface antigens – (glycophorin A would indicate red cells)
* Enzyme expression – (myeloperoxidase, an enzyme, would indicate it is a neutrophil)
The presence of the cell surface antigen glycophorin A would indicate?
The presence of what enzyme would suggest that the cell was a neutrophil?
What techniques are used to identify morphology of cells?
Blood count and blood film
** How can we identify normal progenitor/stem cells? **
What does immunophenotyping look at?
Cell surface antigens e.g CD34
What is the problem with identifying normal progenitor/stem cells?
They are more difficult to recognise as they – microscopically – look the same.
How else (apart from immunophenotyping) can we identify normal progenitor/stem cells?
* Cell culture assays.
* Animal models (not practical in routine diagnostic practice).
** What cell surface antigen do haemopoietic stem cells express? **
What is malignant haemopoiesis characterised by?
Malignant haemopoiesis is usually characterised by:
* Increased numbers of abnormal + dysfunctional cells
* Loss of normal activity
** Increased numbers of abnormal + dysfunctional cells ** is seen in?
Acute leukaemias is a malignancy which affects haemopoiesis
Lymphomas are a malignancy which affects immune function
Malignant haemopoiesis arises due to ONE OR MORE of which 4 things?
1. Increased proliferation.
2. Lack of differentiation.
3. Lack of maturation.
4. Lack of apoptosis.
** Proliferation of abnormal progenitors (precursors) with block in differentiation /maturation ** what condition is this?
Acute leukaemia e.g acute myeloid leukaemia
Describe acute leukaemia.
** Proliferation of abnormal progenitors (precursors) with block in differentiation /maturation **
There is lots of abnormal proliferation with no maturation
Give an example of an acute leukaemia.
Acute myeloid leukaemia
What is the bone marrow filled with in acute leukaemia.
Bone marrow is filled up with primitive cells which proliferate excessively.
The cells are primitive as there is a block of maturation so they cannot divide
Describe the histological appearance of chronic myeloid leukaemia.
Although there is an increase in proliferation, maturation is occurring normally i.e. there are lots of different cell types
Describe the histological appearance of acute myeloid leukaemia.
There is an increase in proliferation, but failure to mature.
Describe chronic myeloproliferative disorders e.g chronic myeloid leukaemia.
Proliferation of abnormal progenitors but NO differentiation/maturation block
** What causes haematological malignancies? **
* Genetic, epigenetic and environmental factors
* Somatic mutations in regulatory genes – driver mutations vs passenger mutations
* Recurrent cytogenetic abnormalities
What are driver mutations?
Mutations in genes which regulate/drive growth
What is a clone?
Population of cells derived from a single parent cell
What are passenger mutations?
Mutations which reflect the noise of mutations which the cell is exposed to
What does the single parent cells (that makes a clone) have?
A genetic marker (driver mutation or chromosomal change) that is shared by the daughter cells.
Can clones diversify?
Yes, but they contain a similar genetic ‘backbone.’