haemopoiesis

Question 1

name the characteristics of a haemopoietic stem cell

Answer 1

• Self-renewal capacity
• Unspecialised
• Ability to differentiate (mature)
• Rare - 1 in 10,000 to 1 in 1 million in bone marrow
• Quiescent (i.e. not undergoing cell cycle, in G0)
– Only undergo occasional cell division

Question 2

what are the three main fates of a stem cell

Answer 2

1. Symmetrical division
   a. Two differentiated cells produced
   b. Contraction of stem cell numbers
2. Symmetrical division
   a. Two stem cells produced
   b. Expansion of stem cell numbers
3. Asymmetrical division
   a. 1 differentiated and 2 stem cell are produced
   b. Maintenance of stem cell numbers

Question 3

what is the stroma

Answer 3

the bone marrow micro-environment that supports the developing haemopoietic stem cell

Question 4

what does an aspirate show you

Answer 4

the cells without the architecture

Question 5

what does a trephine show

Answer 5

this is a core biopsy. It shows the cells within their normal architecture

Question 6

when are haematological malignancies and pre-malignant conditions termed clonal

Answer 6

when they arise from a single ancestral cell

Question 7

how is CML defined

Answer 7

presence of the Philadelphia chromosome

This is a reciprocal translocation between the long arms of chromosomes 9 and 22

Question 8

name 2 classical myeloproliferative disorders

Answer 8

– Polycythaemia rubra vera (PRV)
– Essential thrombocytosis
– Myelofibrosis

Question 9

what mutations are the myeloproliferative disorders associated with

Answer 9

JAK2 and calreticulin

Question 10

what is the pathogenesis of essential thrombocytosis

Answer 10

sustained increased in the platelet count due to megakaryocyte proliferation and overproduction of platelets

Question 11

what are the potential complications of essential thrombosytosis

Answer 11

thrombosis.
May have non-functional platelets leading to haemorrhage
splenomegaly
leukaemia transformation

Question 12

how is essential thrombocytosis treated

Answer 12

low risk - aspirin or anti-platelet agent
intermediate - aspirin +/- hydroxycarbamide
high risk - would try hydroxycarbamide first alongside aspirin and then escalate to anagrelide (inhibits megakaryocyte differentiation)

Question 13

describe myelodysplastic syndromes

Answer 13

• Characterised by increasing bone marrow failure in association with dysplastic changes in one or more lineages.
• Hallmark is the simultaneous proliferation and apoptosis of haematopoietic cells leading to the paradox of hypercellular bone marrow but with pancytopenia in the blood
• May be secondary to previous chemotherapy or radiotherapy
Classically in those who are older.

Question 14

describe how people typically present with myelodysplastic syndromes

Answer 14

majority with fatigue due to the anaemia.
Other are incidenetal.
Others may have infection or bleeding that has been worrying them

Question 15

how would you treat a myelodysplastic syndrome

Answer 15

supportive - blood and platelet transfusion +/- iron chelation.
growth factors
immunosuppression

Question 16

what is an aplastic anaemia

give an example of one

Answer 16

one where there s a pancytopenia resulting from hypoplasia of the bone marrow
Fanconi’s anaemia

Question 17

name some abnormalities often found in Fanconi’s anaemia

Answer 17

• Characterised by increasing bone marrow failure in association with dysplastic changes in one or more lineages.
• Hallmark is the simultaneous proliferation and apoptosis of haematopoietic cells leading to the paradox of hypercellular bone marrow but with pancytopenia in the blood
• May be secondary to previous chemotherapy or radiotherapy

Question 18

how is Fanconis’ anaemia ideally treated ?

what else could you give these patients

Answer 18

allogeneic stem cell transplant

corticosteroids, androgens.

Question 19

How does GVHD often manifest?

Answer 19

skin rash, jaundice or diarrhoea

Question 20

at what time period is it chronic GVHD

Answer 20

100 days after transplant

Question 21

name some issues with SCT

Answer 21

• Limited donor availability, upper age limit <65 years
• Mortality 10-50% depending on risk factors
• Graft versus Host Disease (GVHD)
• Immunosuppression – patients receive high immunosuppression for the first years or so: very prone to infection
• Infertility in both sexes
• Risk of cataract formation
• Hypothyroidism, dry eyes and mouth
• Risk of 2o malignancy
• Risk of osteoporosis / avascular necrosis
• Relapse