Haematopoietic/Myeloid Growth Factors Flashcards

1
Q

Erythropoietin is the most important regulator of…

A

…the proliferation of committed progenitors [Colony Forming Units – CFU- Erythroid (CFU-E)] and their immediate progeny.

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2
Q

Erythropoietin absence leads to…

A

…severe anaemia.

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3
Q

Erythropoiesis is controlled by

A

…a highly responsive feedback system in which a sensor in the kidney detects changes in O2 delivery to modulate EPO secretion.

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4
Q

EPO is encoded by a gene on…

A

…human chromosome 7 expressed primarily in peritubular interstitial cells of the kidney.

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5
Q

EPO contains…

A

193 amino acids with the first 27 cleaved during secretion.

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6
Q

The final hormone is __. What is the molecular mass?

A

heavily glycosylated and has a molecular mass of about 30,000 daltons.

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7
Q

Fate of EPO after secretion

A

It binds on a receptor on the surface of its committed erythroid progenitors in the marrow and is internalized.

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8
Q

Effects of anaemia/hypoxemia on EPO synthesis (Hint: Positive feedback)

A

It results in increased EPO synthesis (greater than 100 fold). This leads to increased serum level of EPO and consequent stimulation of marrow progenitor cells survival, proliferation and maturation.

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9
Q

The regulated feedback loop of EPO can be disrupted by…

A

kidney disease, marrow damage or deficiency in iron/essential vitamin.

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10
Q

EPO secretion, Fe delivery and progenitor proliferation are suppressed by

A

…inflammatory cytokines (produced sequel to infection/inflammatory state.

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11
Q

Epoetin alfa is…

A

…a recombinant human EPO produced using engineered Chinese hamster ovary cells.

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12
Q

Similarities and differences between EPO and epoietin alfa

A

It is nearly identical to the endogenous hormone except for differences in carbohydrate modification pattern and potential to cause pure red cell aplasia.

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13
Q

Epoietin alfa has the potential to cause…

A

pure red cell aplasia.

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14
Q

How was pure red cell aplasia in epoietin alfa observed?

A

This was observed with a commercially available form associated with development of anti-recombinant EPO antibodies which cross-reacts with endogenous EPO.

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15
Q

Epoietin alfa peparations are supplied in single use vials of what measurement…

A

2,000 – 4,000 units/mL

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16
Q

What is Darbapoetin Alfa/ Novel Erythropoiesis – Stimulating Protein (NESP)?

A

A genetically modified form of EPO in which 4 amino acids have been mutated

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17
Q

How does NESP differ from EPO?

A

Differs for Epoetin in that it is a glycosylated form and exhibits a longer half-life

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18
Q

Half life of NESP

A

43 h s.c.

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19
Q

Half life of EPO

A

27 h administered

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20
Q

Therapeutic Uses of EPO Products

A

Anaemias associated

  • poor erythropoietic response e.
  • surgery, AIDS, cancer chemotherapy, prematurity and chronic inflammatory conditions (autoimmune disorders e.g. rheumatoid arthritis and systemic lupus erythematosus).
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21
Q

One condition where poor erythropoietin response is observed is…

A

Chronic kidney disease

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22
Q

EPO products are used in conjunction with…

A

…adequate Fe intake as EPO therapy is associated with absolute or functional Fe deficiency.

23
Q

Relationship between EPO products and iron

A

EPO therapy is associated with absolute or functional Fe deficiency.

24
Q

Effects of epoietin and darbepoetin therapy in patients with anaemia due to cancer and CKD

A

It can increase Hb level, reduce transfusion requirements and improve quality of life.

25
Q

Generally helpful dose for EPO (epoietin alfa) therapy

A

150 units/kg three times a week

26
Q

Full meaning of GM-CSF

A

Granulocyte-Macrophage Colony-Stimulating Factor

27
Q

Synonym for GSF-CSF

A

Colony-Stimulating Factor 2 (CSF 2)

28
Q

Function of GM-CSF/CSF 2

A
  • It stimulates the proliferation, differentiation and function of a number of myeloid cell lineages.
  • It also prevents alveolar proteinosis.
29
Q

Mechanism of action of GM-CSF to increase neutrophil and monocyte production

A

It acts synergistically with Stem Cell Factor (SCF), IL-1, IL-3 and IL-6 to stimulate Colony Forming Unit-Granulocyte- Macrophage (CFU-GM) and Colony Forming Unit- Megakaryocyte (CFU-Meg) to increase neutrophil and monocyte production.

30
Q

GM-CSF acts synergistically with EPO to promote…

A

Burst Forming Unit-Erythrocyte (BFU-E) formation.

31
Q

Difference between progenitor cell and stem cell

A

A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its “target” cell.

Stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times.

32
Q

What is a myeloid cell?

A

They are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets or in a narrower sense also often used, specifically from the lineage of the myeloblast (the myelocytes, monocytes, and their daughter types).

33
Q

Leukocytes are myeloid cells. True or false?

A

False

34
Q

Cells in the myeloid cell line include…

A
Basophils
Neutrophils
Eosinophils
Monocytes
Macrophages
Erythrocytes
Platelets
35
Q

Number of amino acids in recombinant human GM-CSF and its source

A

127 amino acids (glycoprotein); produced in yeast.

36
Q

Another name for GM-CSF

A

Sargramostim

37
Q

Primary therapeutic effect of GM/CSF is

A

the stimulation of myelopoiesis

38
Q

Conditions where the primary effects of GM-CSF/CSF 2 work

A
  • patients undergoing autologous bone marrow transplantation
  • allogenic transplantation
  • patients receiving intensive cancer chemotherapy
  • patients with cyclic neutropenia
  • myelodysplasia
  • aplastic anaemia
  • AIDS associated neutropenia
39
Q

Functions of GSF/CSF 3

A
  • It stimulates proliferation, differentiation and function of neutrophils and their progenitors.
  • It also enhances phagocytic and cytotoxic activities of neutrophils.
  • It also mobilises primitive haemopoietic cells, including haemopoietic stem cells, from marrow to peripheral blood
40
Q

Mechanism of action of GSF/CSF 3

A

It acts primarily on CFU-G, although it also plays a synergistic role with IL-3 and GM-CSF in stimulating other cell lines.

41
Q

Difference between G-CSF/CSF 3 and GM-CSF

A

G-CSF has little effect on monocytes, macrophages and eosinophils, and reduces inflammation by inhibiting IL-1, TNF and interferon gamma.

42
Q

Number of amino acids in recombinant human G-CSF filgrastin

A

175 amino acids (glycoproteins), E. coli.

43
Q

Therapeutic uses of G-CSF/CSF 3

A
  • Different neutropenia type

* Patients undergoing peripheral blood stem cell (PBSC) collection for stem cell transplantation.

44
Q

Types of neutropenia where G-CSF/CSF 3 is administered for treatment

A
  • after autologous haematopoietic stem cell transplantation
  • high dose cancer chemotherapy
  • severe congenital neutropenias
  • cyclic neutropenia
  • neutropenia of AIDS patients receiving zidovudine
45
Q

Thrombopoetin function

A
  • Stimulates self-renewal and expansion of haematopoietic stem cells.
  • Stimulates stem cell differentiation into megakaryocyte progenitors.
  • Selectively stimulates megakaryocytopoiesis to increase platelet production
  • Used to augment peripheral blood (PB) counts in preparation for platelet donation
46
Q

Thrombopoietin acts synergistically with which other growth factors?

A

Especially IL-6 and IL-11

47
Q

TPO size…

A

It is a 45,000 – 75,000 dalton glycoprotein containing 332 amino acids

48
Q

TPO source

A

The liver, marrow stromal cells and many other organs.

49
Q

Genetic elimination of TPO in humans and mice or its receptor reduces platelet counts to 20% of normal values. True or false?

A

Kind of… It’s 10%, actually

50
Q

Forms of recombinant TPO developed for clinical use include…

A

…rHuMGDF (recombinant human megakaryocyte growth and development factor) and rHuTPO (recombinant human thrombopoietin produced in mammalian cells).

51
Q

rHuMGDF is produced in __ and modified with __

A

…bacteria, polyethylene glycol

52
Q

Effect of polyethylene glycol on rHuTPO?

A

Increase circulatory half-life

53
Q

Role of TPO in chemotherapy and radiation-induced myelosuppression

A

It accelerates recovery of platelet counts and other haematological parameters

54
Q

Conditions where TPO offers greater benefits

A
  • Patients with gynaecological cancers receiving carboplatin

- Patients treated with carboplatin plus cyclophosphamide with supplementation with G-CSF and TPO vs. G-CSF alone.