Haematopoiesis Flashcards
What are growth factors?
Polypeptides that control replication and survival vs. death throughout the various stages of blood cell formation
Name the neutrophil precursors
Myeloblasts Promyelocyte Myelocyte Metamyelocyte Band Segmented neutrophil
What is myelopoiesis?
Formation of bone marrow
What are myeloblasts?
Bone marrow progenitor cells
Outline the stages of platelet formation
- DNA replication occurs in megakaryoblasts
- but no cell division
- Megakaryocytes formed
- large polypoid cells
- Cytoplasmic fragments bud off to form platelets
What is lymphopoiesis?
Generation of lymphocytes
Describe the cells needed for initiating blood cell formation
Blood cell formation starts from a small no. of stem cells in bone marrow
–> pluripotent stem cells
–> specific to blood cells and can give rise to early
progenitors
What are the requirements of a bone marrow transplant donor?
Must be (human lymhocyte antigen) HLA matched Can be un/related or autologous (reinfuse patients own bone marrow)
Daily, how many blood cells are produced?
RBCs ~ 2x10¹¹
Neutrophils ~ 5x10¹⁰
Smaller no. of other cell types
There’s a constant high level of blood cells production requiring a lot of cell replication
Describe how a bone marrow transplant works
- Completely ablate haemopoiesis with radiation and
drugs - Infuse compatible donor bone marrow
- Haemopoiesis completely restored
Only haematopoietic stem cells give permanent engraftment - not progenitors or precursors
What are the different types of myeloblasts?
Basophilic myeloblasts
Eosinophilic myeloblasts
What are CSFs?
Colony stimulating factors that stimulate colony growth
e.g. G-CSF (granulocyte-CSF)
Outline the stages of haematopoiesis
early progenitors –> late progenitors –> immature precursors –> mature blood cells
How are lymphocytes formed from stem cells?
Stem cells decide whether to differentiate into lymphocytes or myeloid cells
Once committed to becoming a lymphocyte, stem cells form either:
T- Lymphocytes (in Thymus)
B- Lymphocytes (in Bone marrow)
involving positive feedback loops with the correct transcription factors present
What is erythropoiesis?
Eryhtrocyte formation
Name the different types of CFUs
- CFU-G (neutrophilic granulocyte progenitor)
- CFU-GM (granulocyte/monoprogenitor)
- CFU-E (erythroid progenitor)
- CFU-MK
- CFU-bas
- CFU-eo
How is Haematopoiesis regulated?
Haematopoiesis is regulated by growth factors
Name the precursors of platelet formation
megakaryoblasts –> megakaryocyte –> blood platelets
What are BFU-Es?
Early erythroid progenitors produce colonies that look as though they’ve been burst apart
AKA BFU-E (burst forming unit - erythroid)
How can we examine bone marrow structure?
Using Trephine Biopsy
Aspirate for more detail
- used to examine cellular morphology
- can see both precursors and mature cells
Describe the devlopment of erythrocyte precursors in the bone marrow
As erythrocytes develop, cytoplasm becomes pinker in colour as Hb produced and nucleus becomes smaller
Erythroblasts leave bone marrow, leaving nucleus behind forming RBC
How are T cells formed?
- Early progenitor migrates to thymus once committed to
T cell lineage - T cell receptor gene arrangement
- Positive and negative selection occurs
Where does haematopoiesis occur in the early embryonic state?
Haematopoiesis takes place in the yolk sac
(yolk sac - embryonic structure outside the main embryo) in placenta
What type of process is haematpoiesis?
Irreversible, one way process
What are the risks of Bone marrow transplants?
Mortality while waiting for engraftment
Infection due to neutropenia
Bleeding due to thrombocytopenia
Graft vs Host Disease
Why is it important to measure reticulocyte production in bone marrow?
Increased amount of reticulocytes in marrow means cells are working overtime to produce
RBCs - diagnostic of haemolytic anaemia
What are the applications of Bone Marrow Transplant?
- leukaemia, lymphoma, myeloma
- intensified chemotherapy for solid tmours
- genetic diseases (thalassemia, SCIID etc.)
What is the benefit of stem cells’ individual ability to initiate their own replication?
Acts as an anticancer mechanism
- prevents cells undergoing genetic damage when
replicating including the activation of oncogenes
Ensures most cells that replicate are committed to terminal differentiation
What are the important features of progenitors?
Undifferentiated
- unidentifiable morphologically as no mature cell
characteristics present yet
Committed
- Already committed to which mature cells they’ll
generate
How does B cell formation occur?
- Immunoglobulin gene rearrangement occurs
- Expression of surface immunoglobulin (IgM) on
membrane - Immature B cells migrates to secondary lymphoid
organs for maturation & antigen selection
What are immature red blood cells called?
Reticulocytes
Describe how colony assays can be used to grow a colony of mature cells
- Growth factors in semi solid medium (agar)
- A progenitor cell with correct growth factor will grow
into a colony of one lineage - Progenitors grow to form mature cell colonies from 32-
1000’s of cells
- progenitors are therefore also known as Colony Forming Units (CFUs)
What is the role of stem cells in mice?
- Mark cells via retrovirus insertion
- Transplant irradiated mice with small no. of stem cells
- Same marked stem cells give rise to neutrophils,
lymphocytes etc.
In a foetus, where does haematopoiesis occur?
In the foetal liver - very red haematical vital organ
How can stem cells cause leukaemia in humans?
Can cause chronic myeloid leukaemia (CML) caused by a chromosome translocation on small chromosome 22 and large 23
found in T cell lineages
most produce excess neutrophils
Stimulates myeloid cell production
What are the advantages of Bone marrow transplant?
Only curative treatment available for many diseases
During infancy where does haematopoiesis happen?
Occurs throughout the bone marrow
What type of stem cells are haematopoietic cells?
Pluripotent and self maintaining
Outline how blood cells are formed
Stem cells -> progenitors -> precursors -> mature blood cells
List some G-CSF applications
- neutrophil recovery after BMT/chemo
- hereditary neutropenia
- stimulates platelet recovery as stimulates other lineages
(only in combination with other growth factors)
When do blood cells become differentiable?
Stem cells & progenitors can’t be distinguished morphologically as there is no real difference between them
Precursors begin looking like mature cells
Mature cells are easily identifiable via their morphology
How do haematopoietic growth factors work?
Cytokines (polypeptides) bind to cell surface membrane receptors
Stimulating growth and progenitor survival
What is erythropoietin?
EPO is a hormone produced in the kidney, in response to hypoxia
How are stem and progenitor cells purified?
Stem cells and early progenitors carry cell surface antigen CD34 used to purify them
Where does blood cell formtaion occur in adults?
Haematopoiesis is limited to the central skeleton under normal conditions which includes:
- vertebrae
- ribs & sternum
- skull
- sacrum
- pelvis
- proximal ends of humerus & femur
What is the advantage of Peripheral blood stem cell transplantation?
Less traumatic alternative to bone marrow transplantation , no general anaesthetic needed
What is the role of eryhtropoietin?
Increases RBC production via increase of progenitor survivor using CFU-E
Speciifc to lineage; acts on late progenitors
When are G-CSF produced?
Granulocyte colony stiumlating factors are produced by many cell types in response to inflammation
What are the different types of blood vessels?
Red marrow - Active haematopoiesis - contains lots of eyrhtrocytes
Yellow marrow - filled with fat cells
What is haematopoiesis?
Formation of blood cells
How is G-CSF used in peripheral blood stem cell transplantation?
G-CSF causes stem cells to be released from the bone marrow into circulation
Seen by appearnce of CD34 and cells in circulation
Collected by leukapheresis
What are the clinical applications of recombinant erythropoietin?
- Treatment of anaemia kidney failure
- Alternative to blood transfusion
What is bone marrow?
A spongy jelly like tissue inside the bone that is highly metabolically active
Contains many blood vessels to bring nutrients in and take away new blood vessels
How do G-CSFs work?
Acts on mature neutrophils in periphery as a chemoattractant promoting neutrophil
activation and maturation.
Also stimulates neutrophil production in bone marrow by stimulating neutrophil progenitors CFU-G
