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Week 3 - haematology > Haemopoiesis > Flashcards

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
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2
Q

What is the site of haemopoiesis in an infant?

A

Bone marrow of all bones

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3
Q

What is the site of haemopoiesis in adults?

A 
Bone marrow - central skeleton 
•Vertebrae 
•Ribs 
•Sternum 
•Skull 
•Sacrum 
•Ends of femurs
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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
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5
Q

Which cells are made from lymphoid cells

A
  • Lymphocytes -> plasma cell

* NK cells

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6
Q

What are the characteristics of haeompoietic stem cells?

A
  • Self renewal capacity
  • Unspecialised
  • Ability to differentiate
  • Quiescent (in G0)
  • Rare
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7
Q

What are the characteristics of haeompoietic stem cells?

A
  • Self renewal capacity
  • Unspecialised
  • Ability to differentiate
  • Quiescent (in G0)
  • Rare
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8
Q

Where are haemopoietic stem cells found?

A
  • Bone marrow
  • Peripheral blood after treatment with G-CSF
  • Umbilical cord blood
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9
Q

What are the different lifecycle options for haemopoietic stem cells?

A
  • Differentiation (maturation and specialisation)
  • Apoptosis - programmed cell death
  • Self renewal
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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
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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
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12
Q

What are the stromal cells?

A
  • Macrophages
  • Fibroblasts
  • Endothelial cells
  • Fat cells
  • Reticulum cells
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13
Q

What supports the stromal cells?

A 
An extracellular matrix:
•Collagen 
•Haemonectin 
•Proteoglycans 
•Laminin 
•Fibronectin
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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
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15
Q

What are the hereditary conditions impairing bone marrow function?

A
  • Thalassaemia
  • Sickle cell anaemia
  • Fanconi anaemia
  • Hereditary leukaemia
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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
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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
Q

What is an autologous transplant?

A

Uses the patients own blood stem cells

26
Q

What is an allogenic transplant?

A

Any transplant in which the stem cell come from a donor

27
Q

In an allogenic stem cell transplant, what are the types of donor?

A
  • Syngenic - identical twin
  • Allogenic - HLA identical
  • Haplotype identical - half matched family member
  • Volunteer unrelated
  • Umbilical cord blood
28
Q

What are the main indications for an autologous stem cell transplant?

A
  • Relapsed Hodgkin’s disease
  • Non Hodgkins lymphoma
  • Myeloma
29
Q

How are autologous stem cell transplants carried out?

A
  • 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
Q

How do they get stem cells from cord blood?

A
  • 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
Q

What are the advantages of cord blood stem cell transplants?

A
  • More rapidly available than volunteer unrelated

* Less rigorous matching to patient type of patient as immune system naive

32
Q

What are the disadvantages of cord blood stem cell transplants?

A
  • 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
Q

How do they do allogenic stem cell transplants?

A
  • Can use peripheral blood stem cells, bone marrow or umbilical cord blood
  • May be full intensity ‘myeloablative’ or reduced intensity ‘mini’ transplant
34
Q

What are the main indications of an allogenic stem cell transplantation?

A
  • Acute and chronic leukaemias
  • relapsed lymphoma
  • Aplastic anaemia
  • hereditary disorders
35
Q

What are the problems with stem cell transplants?

A
  • 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
Q

What can myelodysplastic syndromes be secondary to?

A

Previous chemo or radiotherapy

37
Q

What can the myelodysplatic syndromes progress to?

A

Acute myeloid leukaemia

38
Q

What is seen in refractory anaemia?

A
  • Excess blasts

* Ring sideroblasts

39
Q

What chromosomal abnormality is associated with refractory anaemia?

A

Monosomy 7

40
Q

What mutations are the classical myeloproliferative disorders associated with?

A
  • JACK2V617F

* Calrecticulin

Week 3 - haematology (17 decks)

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