Haemopoiesis Flashcards
1
Q
What are the sites of haemopoiesis in the foetus?
A
- 0-2 months: yolk sac
- 2-7 months: liver, spleen
- 5-9 months: bone marrow
2
Q
What is the site of haemopoiesis in an infant?
A
Bone marrow of all bones
3
Q
What is the site of haemopoiesis in adults?
A
Bone marrow - central skeleton •Vertebrae •Ribs •Sternum •Skull •Sacrum •Ends of femurs
4
Q
Which cells are made from myeloid stem cells (end)
A
- Erythrocytes
- Platelets (from megakaryocytes)
- Macrophages (mono blast -> monocyte)
- Neutrophils (from myeloblast)
- Eosinophils
- Mast cell
5
Q
Which cells are made from lymphoid cells
A
- Lymphocytes -> plasma cell
* NK cells
6
Q
What are the characteristics of haeompoietic stem cells?
A
- Self renewal capacity
- Unspecialised
- Ability to differentiate
- Quiescent (in G0)
- Rare
7
Q
What are the characteristics of haeompoietic stem cells?
A
- Self renewal capacity
- Unspecialised
- Ability to differentiate
- Quiescent (in G0)
- Rare
8
Q
Where are haemopoietic stem cells found?
A
- Bone marrow
- Peripheral blood after treatment with G-CSF
- Umbilical cord blood
9
Q
What are the different lifecycle options for haemopoietic stem cells?
A
- Differentiation (maturation and specialisation)
- Apoptosis - programmed cell death
- Self renewal
10
Q
describe the ways in which stem cells change their numbers or maintain them
A
- Symmetrical division: contraction of stem cell numbers- cells differentiate
- Symmetrical divison: expansion of stem cell numbers - identical copies are made
- Asymmetrical division: maintenance of stem cell numbers, one cell will differentiate and the other will be a copy
11
Q
In bone marrow, what is the stroma?
A
- The microenvironment that supports the developing haemopoietic cell
- It is a rich environment for the growth and development of stem cells
12
Q
What are the stromal cells?
A
- Macrophages
- Fibroblasts
- Endothelial cells
- Fat cells
- Reticulum cells
13
Q
What supports the stromal cells?
A
An extracellular matrix: •Collagen •Haemonectin •Proteoglycans •Laminin •Fibronectin
14
Q
What are the acquired conditions that impair bone marrow function?
A
- aplastic anaemia
- leukaemia
- myelodysplasia
- myeloproliferative disorders
- lymphoproliferative disorders
- myelofibrosis
- metastatic malignancy e.g. breast, prostate
- infections e.g. TB/HIV
- Drugs and toxins
- Chemotherapy
- Haematinic deficiency
15
Q
What are the hereditary conditions impairing bone marrow function?
A
- Thalassaemia
- Sickle cell anaemia
- Fanconi anaemia
- Hereditary leukaemia
16
Q
Describe leukaemogenesis
A
- A multi step process in which a haemopoietic stem cell or an early myeloid or lymphoid cell undergoes a leukaemogenic event
- This results in dysregulation of growth and differentiations which are often associated with mutations
- Proliferation of the leukaemic clone occurs with the differentiation blocked at an early age
- the clonogenic leukaemia cells have a growth advantage over the normal haemopoietic cells so suppress the normal bone marrow
17
Q
When are haematological malignancies classed as clonal?
A
If they arise from a single ancestral cell
18
Q
What is the evidence of clonality?
A
- Most lymphoproliferative disorder and some acute myeloid leukaemias carry a unique rearrangement of an immunoglobulin or TcR (T cell receptor)
- X chromosome inactivation studies in women with leukaemia show that clonal proliferation carries either an active maternal or paternal X chromosome
- Acquired cytogenetic or molecular changes that arise during the development of a malignancy
19
Q
What are the classical myeloproliferative disorders?
A
- Polycythaemia rubra vera
- essential thrombocytosis
- myelofibrosis
20
Q
What are the other (non-classical) myeloproliferative disorders?
A
- Mastocytosis
- Clonal hypereosinophilic syndromes
- Chronic neutrophilic leukaemia
21
Q
What are the myelodysplastic syndromes characterised by?
A
- Dysplasia and ineffective haemopoiesis in >/ 1 of the myeloid series (RBC/platelets/WBCs)
- Often associated with acquired cytogenic abnormalities
- Majority are characterised by progressive bone marrow failure
22
Q
What are the characteristics of fanconi anaemia?
A
- somatic abnormalities
- Bone marrow failure
- Short telomeres
- Malignancy
- Chromosome instability
23
Q
What is the inheritance of fanconi anaemia?
A
Autosomal recessive
24
Q
What are the clinical signs of Fanconi anaemia?
A
- microphthalmia
- GU malformations
- GI malformations
- Mental retardation
- Hearing loss
- CNS effects e.g. hydrocephalus
25
What is an autologous transplant?
Uses the patients own blood stem cells
26
What is an allogenic transplant?
Any transplant in which the stem cell come from a donor
27
In an allogenic stem cell transplant, what are the types of donor?
* Syngenic - identical twin
* Allogenic - HLA identical
* Haplotype identical - half matched family member
* Volunteer unrelated
* Umbilical cord blood
28
What are the main indications for an autologous stem cell transplant?
* Relapsed Hodgkin's disease
* Non Hodgkins lymphoma
* Myeloma
29
How are autologous stem cell transplants carried out?
* Almost all use mobilised peripheral blood stem cells harvested by apheresis
* Patients receive growth factor (G-CSF) +/- chemotherapy to make the stem cells leave the bone marrow so they can be collected from the blood
* Mozobil can be used in those that have failed to mobilise
30
How do they get stem cells from cord blood?
* Blood stem cells are collected from the umbilical cord and placenta
* Cells are tissue types and frozen in liquid nitrogen in cord blood banks
31
What are the advantages of cord blood stem cell transplants?
* More rapidly available than volunteer unrelated
| * Less rigorous matching to patient type of patient as immune system naive
32
What are the disadvantages of cord blood stem cell transplants?
* Small amount so adults will often require double cord transplant
* Slower engraftment
* If the patient relapses, cannot go back for DLI (donor lymphocyte infusion)
33
How do they do allogenic stem cell transplants?
* Can use peripheral blood stem cells, bone marrow or umbilical cord blood
* May be full intensity 'myeloablative' or reduced intensity 'mini' transplant
34
What are the main indications of an allogenic stem cell transplantation?
* Acute and chronic leukaemias
* relapsed lymphoma
* Aplastic anaemia
* hereditary disorders
35
What are the problems with stem cell transplants?
* limited donor availability, upper age limit of 65 years
* mortality is 10-50% depending on risk factors
* Graft vs host disease
* Immunosuppression
* Infertility in both sexes
* Risk of cataract formation
* Hypothyroidism, dry eyes and mouth
* Risk of a secondary malignancy
* Risk of osteoporosis/ avascular necrosis
* relapse
36
What can myelodysplastic syndromes be secondary to?
Previous chemo or radiotherapy
37
What can the myelodysplatic syndromes progress to?
Acute myeloid leukaemia
38
What is seen in refractory anaemia?
* Excess blasts
| * Ring sideroblasts
39
What chromosomal abnormality is associated with refractory anaemia?
Monosomy 7
40
What mutations are the classical myeloproliferative disorders associated with?
* JACK2V617F
| * Calrecticulin
