Week- concepts of malignancy in haematology Flashcards
What is the only cell that comes from both myeloid and lymphoid lineage?
Dendritic cells.
How can you identify more mature cells in the blood (methods)?
Can look at morphology- e.g. structure of the nucleus, things in the cytoplasm etc. Cell surface antigens e.g. glycophorin A- for red cells Enzyme expression-e.g. myeloperoxidase inhibitors= neutrophils
Which colour granules do eosinophils have?
Red granules
Which colour granules do neutrophils have?
Blue granules.
What do neutrophils look line under a microscope?
Multisegmented nucleus
Blue granules
What do eosinophils look like under the microscope?
Red granules.
Bilobed nucleus.
How can we identify normal stem cells/progenitor cells?
Cell surface antigens (immunophenotyping)
Cell culture assays and animal models (not routinely used)
What occurs in malignant haemopoeisis?
Usually characeterised by increased number of abnormal and dysfunctional cells and loss of normal activity.
What are the ways in which their can be increased numbers of abnormal and dysfunctional cells?
Increased proliferation
Lack of differentiation
Lack of maturation
Lack of apoptosis.
NOTE- dont need all of these characteristics to be considered malignant.
There are two scenarios in which malignancies can occur. Can you describe these in terms of myeloid leukaemias?
On the left-
There is proliferation of abnormal progenitors with a block in maturation (meanign you have lots of immature cells)
e.g. acute myeloid leukaemia.
On the right-
Proliferation of abnormal progenitors with no block in maturation (meaning you have lots of normal looking mature cells)
e.g. chronic myeloid leukaemias
This is what normal bone marrow looks like, how will someone with acute leukaemias marrow differ? (think of the cells present in acute myeloid leukaemia)
There will be lots of immature (therefore large) and not differentiated cells.
This is what normal bone marrow looks like, how will someone with chronic leukaemias marrow differ? (think of the cells present in acute myeloid leukaemia)
There will be lots of cells present like in acute ones, however also there will be mature cells (e.g. neutrophils as seen in this slide).
What causes haematological malignancies?
Genetics
Somatic mutations in regulatory genes (driver genes- mutations in genes that control growth).
Recurrent cytogenetic abnormalities (e.g. deletions, chromosonal translocations). They are not causative however do contribute.
What is meant by the term clones?
A population of cells derived from a single parent cell.
How is normal haemopoeisis described in terms of ‘clones’?
Polyclonal- coming from several cells.
How is malignant haemopoesis described in terms of clones?
Monoclonal- derived from one cell.
NOTE- means that in malignancy, you tend to just see proliferation of one cell type whereas in normal haemopoesis you see lots of cell types.
What is meant by a driver mutation?
A mutation in a gene that provides a selective growth advantage.
What is meant by passenger mutations?
These are mutations that do not confer a selective growth advantage. However they will be present in cancers.
NOTE-
Acquiring cancer-
As you grow up you acquire passenger mutations. These do not affect cell growth and therefore do not cause cancer (as cancer is uncontrolled cell growth). However as soon as you acquire a driver mutation (these affect cell growth) it becomes problematic. You can get uncontrolled proliferation, lack of apoptosis, lack of maturation or differentiaion due to these.
NOTE-
Acute lymphoblastic leukaemia- they looked at a child of age 10 who had this disease, and then looked back at her Guthrie card to see if the mutation was present at birth. They found that it was, therefore the initial ‘hit’ was present at birth, however more mutations were acquired throughout life making the child acquire the cancer.
NOTE- driver mutations are present frequently BUT only some go on to confer cancer.
How can haematological malignancies be categorised?
Based on cell lineage
Based on developmental stage
Based on anatomical site involved.
If the malignancy is based on cell lineage, what can the cells be?
Either myeloid or lymphoid.
NOTE- lymphoid means lymphocytes so B cells, T cells, NK cells, dendritic cells
Myeloid means it could be RBCs, granulocytes or dendritic cells.
If the cell involved is primitive, what can it be called? Use the example of a lymphocytic malignancy?
Lymphoblastic (blast means immature)
If the cell involved is mature, what can it be called? Use the example of a lymphocytic malignancy?
Lymphocytic
