Chapter 44: Hematopoesis/Immunomodulation

Question 1

What interleukins activate the myeloid line?

Answer 1

IL-3, IL-6

Question 2

What interleukin activates CFU-Mix (the mega/erythro pathway)?

Answer 2

IL-11

Question 3

What interleukins activate the T cell line of lymphoid stem cells?

Answer 3

IL-7

Question 4

What interleukins activate the NK line of lymphoid stem cells?

Answer 4

IL-15

Question 5

What activates the B cell line of lymphoid stem cells?

Answer 5

Flt3L

Question 6

What induces erythropoietin expression?

Answer 6

• JAK2-activating mutations, HIF-1alpha

Question 7

What turns off erythropoietin production?

Answer 7

• turned off by PHD (prolyl hydroxylase) adding an OH group to HIF-1alpha during high oxygen/CO conditions, leading it to bind to VHL complex to be tagged for proteosomal degradation

Question 8

What is mutated in Chuvash polycythemia )familial erythrocytosis 2)?

Answer 8

VHL complex, so that HIF-1alpha-OH can’t be degraded, leading to increased erythropoietin

Question 9

What interleukins activate that general lymphoid stem cell pathway?

Answer 9

IL-2, IL-7

Question 10

What growth factors are activate in the early stages vs. the late stages of platelet production? What prevents overproduction?

Answer 10

early: IL-11.
late: TPO , IL-6.
Prevents overproduction: Mpl (thrombopoeitin receptor)

Question 11

What are some side effects or erythropoietin and darbepoietin?

Answer 11

cardiac arrythmia, MI, HTN, polycythemia

Question 12

Which has a a longer half life and why, erythropoietin or darbepoietin?

Answer 12

darbepoietin: more sialic acid groups

Question 13

What are the two demethylizing agents for sickle cell/myelodysplastic syndromes, causing fetal hemoglobin production in adults?

Answer 13

5-azacytidine, decitabine

Question 14

What drug blocks the division of HbS-expressing erythroid precursors, inhibiting ribonucleotide reductase and leading to increased HbF?

Answer 14

hydroxyurea

Question 15

What treats sickle cell, polycythemia versa, and refractory CML, but can lead to secondary leukemia?

Answer 15

hydroxyurea

Question 16

What drugs prevent the switch from HbF to HbA by inhibiting histone deacetylases?

Answer 16

butyrates

Question 17

What treats neutropenia by increasing just granulocyte precursors and enhancing their microbicidal activity for infection combat, but can cause bone pain, vasculitis, and precip. sickle crisis?

Answer 17

filgastrim (rhG-CSF) and PEG-filgastrim (“fil goes halfway”)

Question 18

What treats neutropenia/infection combat by increasing granulocyte and monocyte precursors?

Answer 18

sargamostim (rhGM-CSF)

(“sergants = go all the way”)

Question 19

What is the mechanism of rhTPO and PEG-rHuMGDF?

Answer 19

Prevent chemo-induced thrombocytopenia by binding to and activating MpI (thrombopoietin receptor)

Question 20

What are the two treatments for idiopathetic TTP, and which is a TPO receptor agonist and which is a recomb Fc peptide fusion protein?

Answer 20

elTrOmbopag: TPO receptor agonist.
romiplostim: recomb Fc peptide fusion protein

Question 21

What treats chemotherapy-induced thrombocytopenia with side effects of fluid retention, a. fib, and fatigue?

Answer 21

oprelvekin (rh IL-11)

Question 22

What treats colon cancer in combo with 5-FU by causing macrophages and T-cells to secrete cytokines to supress tumor growth?

Answer 22

levamisole

Question 23

What treats melanoma?

Answer 23

IL-2

Question 24

What treats acute promyelocytic leukemia and acne by allowing differentiation of promyelocytic cells into normal granulocytes?

Answer 24

tretinoin