Haematological malignancy (intro) Flashcards
Give an overview of the epidemiology of blood cancer, concerning:
a) age groups
b) gender
Blood cancers account for 11% of all cancers
Affects all ages, including children (ALL is most common cancer of children)
Adult males are more commonly affected than females
Describe the genetic alterations that occur in the pathogenesis of haematological malignancies
In order for malignancies to occur - there must be an accumulation of acquired genetic alterations in long lived cells (stem cells)
These mutations cause a proliferative/survival advantage so the malignant clone (developing group of mutated cells) grows to dominate the tissue
The 2 key features of stem cells is that they are:
- self-renewing
- pluripotent
What do these mean?
Self-renewing:
- When stem cell divide, one remaines a stem cell and one differentiates so there is always a remaining pool of stem cells
Pluripotent:
- Stem cells can give rise to any cell (so a haematopoeitic stem cell can give rise to any blood cell)
What are the 2 primary groups of haematological malignancies?
Myeloid malignancies and lymphoid malignancies
Myeloid malignancies - all of the blood cancers that involve:
- RBCs
- platelets
- granulocytes
- monocytes
Lymphoid malignancies - all of the blood cancers that involve:
- T lymphocytes
- B lymphocytes
- NKCs
What group of blood cancers are caused by stem cell mutations making progenitor cells unable to differentiate?
What are the 2 types of this?
Acute leukaemias
Acute myeloid leukaemia (AML) - inability of myeloid progenitor cells to differentiate (diagram)
Acute lymphoblastic leukaemia (ALL) - inability of lymphoid progenitor cells to differentiate
In Acute myeloid leukaemia, what will the population of cells be like?
Myeloid progenitor cells proliferate but cant differentiate - so there is a production of useless cells - called Blast cells
This means there will be low numbers of:
- RBCs
- Granulocytes (neutrophils, eosinophils, basophils)
- Monocytes (macrophages)
- Platelets
- Mast cells
In acute myeloid leukaemia, where do the blast cells accumulate?
In the bone marrow
How do myeloproliferative disorders differ from acute myeloid leukaemia?
Give an example of a myeloproliferative disorder
In myeloproliferative disorders, the stem cell mutations allow the myeloid progenitor cells to proliferate but also differentiate (grow up) but abnormally
This means the end product cells (RBCs, neutrophils etc) are produced - but in huge numbers and abnormal proportions
Example of myeloproliferative disorder = Chronic myeloid leukaemia (CML)
What causes acute lymphoblastic leukaemia (ALL)?
What happens to the population of blood cells in ALL
When mutations in the stem cells prevent lymphoid progenitor cells from differentiating (but they still proliferate) - similar to AML
There is an accumulation of Blast cells (which are visually identical to blast cells in AML) which do not differentiate into lymphocytes
What is the collective name for malignancies affecting mature lymphoid cells
What are the 3 groups of diseases that this includes?
Mature lymphoid malignancies:
- Chronic lymphocytic leukaemia (CLL)
- Lymphomas
- Multiple myeloma (MM)
Leukaemia and lymphoma are terms used to describe the distribution of the disease (cancer) in the body
Where are leukaemias located and where are lymphomas located?
Is there any cross over?
Leukaemias - blood and bone marrow
Lymphomas - lymph nodes or other organs (eg liver)
Occasionally - diseases which are histologically leukaemias can manifest as lymphomas and vice-versa
An example of this is Acute lymphoblastic leukaemia (ALL) which can occasionally present with the disease located in the thymus in which case it is called lymphoblastic lymphoma
Lymphoma, particularly B cell lymphoma, arises due to mutations which occur when and where and how?
Lymphoma is covered more in immunology
Occurs during B cell maturation in the Germinal centres of lymph nodes
During maturation - there is a lot of genetic recombination and this can allow unwanted and malignancy causing mutations to occur
Lymphadenopathy is a very common and can be due to a number of different things. The nature of the swelling (eg painful and localised) can give indications to the cause
What problems are indicated by lymphadenopathy that is:
a) localised & painful
b) localised & painless
c) generalised & painful/tender
d) generalised & painless
Localised and painful:
- bacterial infection in draining site
Localised and painless:
- rare infections
- metastatic carcinoma (hard lymph node)
- lymphoma (rubbery)
Generalised and painful/tender:
- viral infections - EBV, CMV, Hep, HIV
Generalised and painless:
- lymphoma (rubbery)
- leukaemia
- connective tissue disease - eg sarcoidosis
- drugs
