Haematopoiesis Flashcards
Where are the sites of haematopoiesis
Foetus: 0-2 months its the yolk sack. 2-7months its the liver and spleen. Then 5-9months its the bone marrow.
Infants: Bone marrow of all bones.
Adults: Bone marrow of ends of femurs, vertebrae, ribs, sternum, sacrum, skull and pelvis
Describe the characteristics of haemopoietic stem cells
- Have the capacity to self renew,
- Unspecialised,
- Ability to differentiate (mature) into myeloid stem cells or lymphoid stem cells.
- Rare,
- Quiescence (not undergoing replication) and only occasionally undergo replication
What are the different fates of a haematopoietic stem cell?
- Self renewal (forms identical copy),
- Apoptosis,
- Differentiation (Myeloid stem cell which will form cells like erythrocytes, platelets, neutrophils etc. Or lymphoid stem cell which will form the precursors for B and T cells)
What controls stem cell fate?
Complex interplay of micro-environmental signals and internal cues
What is the Stroma and what does it consist of?
It is the bone marrow microenvironment that supports the developing haematopoietic cell. Stromal cells include macrophages, fibroblasts, endothelial cells, fat cells and reticulum cells. These cells are supported by the extracellular matric which consists of fibronectin, haemonectin, collagen, proteoglycans and laminin.
Name some examples of Hereditary bone marrow dysfunctions
-Thalassaemia,
- Sickle cell anaemia,
- Fanconi anaemia,
- Dyskeratosis congentia,
- Diamon-Blackfan anaemia
Name some example of acquired bone marrow diseases
- Aplastic anaemia,
- Leukaemia,
- Myelodysplasia,
- Myeloproliferative disorders,
- Lymphoproliferative disorders,
- Myelofibrosis,
- Metastatic malignancy,
- Infections,
- Drugs and toxins
What are the principles of leukaemogenesis?
It is a multistep process which results in the dysregulation of cell growth and differentiation, following a leukaemogenic event. Resulting in leukaemia blast cells
Haematological malignancies and pre-malignant conditions are termed what if they arise from a single ancestral cells
Clonal
What are myeloproliferative disorders and some examples?
Clonal disorders which result in increased numbers of one or more mature blood cells.
Classical MPDs - Polycythemia rubra veram essential thrombocytosis and myelofibrosis. These are variably associated with the JAK2 gene and CALR (calreticulin) mutation. (all have potential to transform into AML).
What are myelodysplastic syndromes?
Characterised by dysplasia (abnormal cells which may become cancerous) and ineffective haemopoiesis in at least 1 of the myeloid series.
Examples = Refractory anaemia with excess blasts or monosomy 7
They may occur secondary to previous chemo/radiotherapy. Often associated with genetic abnormalities
Majority are characterised by progressive bone marrow failure and some can progress to AML
What is Fanconi anaemia?
Autosomal recessive disease in the FANCA-G gene which accounts for 10-20% of aplastic anaemia cases. Under production of RBCs.
Inherited cause of aplastic anemia
What are the characteristics of fanconi anaemia?
- Bone marrow failure,
- Short telomeres,
- Malignancy,
- Chromosome instability,
- Short stature,
- Microphthalmia,
- GU and GI malformations,
- Mental retardation,
- Hearing loss,
- Hydrocephaly
What is the molecular biology of Fanconi anaemia?
The fanconi mutation results in altered DNA damage responses, abnormal oxidative stress response, upregulation of molecules and defective telomeres. This along with environmental factors causes genomic instability and ultimately cancer
What are the different types of stem cell transplantations
- Autologous transplant (used patients own blood),
- Allogeneic transplant (uses donor stem cells)
