Haemopoiesis Flashcards
What are the sites of haemopoiesis in the foetus?
- 0-2 months: yolk sac
- 2-7 months: liver, spleen
- 5-9 months: bone marrow
What is the site of haemopoiesis in an infant?
Bone marrow of all bones
What is the site of haemopoiesis in adults?
Bone marrow - central skeleton •Vertebrae •Ribs •Sternum •Skull •Sacrum •Ends of femurs
Which cells are made from myeloid stem cells (end)
- Erythrocytes
- Platelets (from megakaryocytes)
- Macrophages (mono blast -> monocyte)
- Neutrophils (from myeloblast)
- Eosinophils
- Mast cell
Which cells are made from lymphoid cells
- Lymphocytes -> plasma cell
* NK cells
What are the characteristics of haeompoietic stem cells?
- Self renewal capacity
- Unspecialised
- Ability to differentiate
- Quiescent (in G0)
- Rare
What are the characteristics of haeompoietic stem cells?
- Self renewal capacity
- Unspecialised
- Ability to differentiate
- Quiescent (in G0)
- Rare
Where are haemopoietic stem cells found?
- Bone marrow
- Peripheral blood after treatment with G-CSF
- Umbilical cord blood
What are the different lifecycle options for haemopoietic stem cells?
- Differentiation (maturation and specialisation)
- Apoptosis - programmed cell death
- Self renewal
describe the ways in which stem cells change their numbers or maintain them
- 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
In bone marrow, what is the stroma?
- The microenvironment that supports the developing haemopoietic cell
- It is a rich environment for the growth and development of stem cells
What are the stromal cells?
- Macrophages
- Fibroblasts
- Endothelial cells
- Fat cells
- Reticulum cells
What supports the stromal cells?
An extracellular matrix: •Collagen •Haemonectin •Proteoglycans •Laminin •Fibronectin
What are the acquired conditions that impair bone marrow function?
- 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
What are the hereditary conditions impairing bone marrow function?
- Thalassaemia
- Sickle cell anaemia
- Fanconi anaemia
- Hereditary leukaemia
Describe leukaemogenesis
- 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
When are haematological malignancies classed as clonal?
If they arise from a single ancestral cell
What is the evidence of clonality?
- 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
What are the classical myeloproliferative disorders?
- Polycythaemia rubra vera
- essential thrombocytosis
- myelofibrosis
What are the other (non-classical) myeloproliferative disorders?
- Mastocytosis
- Clonal hypereosinophilic syndromes
- Chronic neutrophilic leukaemia
What are the myelodysplastic syndromes characterised by?
- 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
What are the characteristics of fanconi anaemia?
- somatic abnormalities
- Bone marrow failure
- Short telomeres
- Malignancy
- Chromosome instability
What is the inheritance of fanconi anaemia?
Autosomal recessive
What are the clinical signs of Fanconi anaemia?
- microphthalmia
- GU malformations
- GI malformations
- Mental retardation
- Hearing loss
- CNS effects e.g. hydrocephalus
What is an autologous transplant?
Uses the patients own blood stem cells
What is an allogenic transplant?
Any transplant in which the stem cell come from a donor
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
What are the main indications for an autologous stem cell transplant?
- Relapsed Hodgkin’s disease
- Non Hodgkins lymphoma
- Myeloma
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
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
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
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)
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
What are the main indications of an allogenic stem cell transplantation?
- Acute and chronic leukaemias
- relapsed lymphoma
- Aplastic anaemia
- hereditary disorders
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
What can myelodysplastic syndromes be secondary to?
Previous chemo or radiotherapy
What can the myelodysplatic syndromes progress to?
Acute myeloid leukaemia
What is seen in refractory anaemia?
- Excess blasts
* Ring sideroblasts
What chromosomal abnormality is associated with refractory anaemia?
Monosomy 7
What mutations are the classical myeloproliferative disorders associated with?
- JACK2V617F
* Calrecticulin
