Chapter 44: Hematopoesis/Immunomodulation Flashcards
What interleukins activate the myeloid line?
IL-3, IL-6
What interleukin activates CFU-Mix (the mega/erythro pathway)?
IL-11
What interleukins activate the T cell line of lymphoid stem cells?
IL-7
What interleukins activate the NK line of lymphoid stem cells?
IL-15
What activates the B cell line of lymphoid stem cells?
Flt3L
What induces erythropoietin expression?
- JAK2-activating mutations, HIF-1alpha
What turns off erythropoietin production?
- 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
What is mutated in Chuvash polycythemia )familial erythrocytosis 2)?
VHL complex, so that HIF-1alpha-OH can’t be degraded, leading to increased erythropoietin
What interleukins activate that general lymphoid stem cell pathway?
IL-2, IL-7
What growth factors are activate in the early stages vs. the late stages of platelet production? What prevents overproduction?
early: IL-11.
late: TPO , IL-6.
Prevents overproduction: Mpl (thrombopoeitin receptor)
What are some side effects or erythropoietin and darbepoietin?
cardiac arrythmia, MI, HTN, polycythemia
Which has a a longer half life and why, erythropoietin or darbepoietin?
darbepoietin: more sialic acid groups
What are the two demethylizing agents for sickle cell/myelodysplastic syndromes, causing fetal hemoglobin production in adults?
5-azacytidine, decitabine
What drug blocks the division of HbS-expressing erythroid precursors, inhibiting ribonucleotide reductase and leading to increased HbF?
hydroxyurea
What treats sickle cell, polycythemia versa, and refractory CML, but can lead to secondary leukemia?
hydroxyurea
What drugs prevent the switch from HbF to HbA by inhibiting histone deacetylases?
butyrates
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?
filgastrim (rhG-CSF) and PEG-filgastrim (“fil goes halfway”)
What treats neutropenia/infection combat by increasing granulocyte and monocyte precursors?
sargamostim (rhGM-CSF)
(“sergants = go all the way”)
What is the mechanism of rhTPO and PEG-rHuMGDF?
Prevent chemo-induced thrombocytopenia by binding to and activating MpI (thrombopoietin receptor)
What are the two treatments for idiopathetic TTP, and which is a TPO receptor agonist and which is a recomb Fc peptide fusion protein?
elTrOmbopag: TPO receptor agonist.
romiplostim: recomb Fc peptide fusion protein
What treats chemotherapy-induced thrombocytopenia with side effects of fluid retention, a. fib, and fatigue?
oprelvekin (rh IL-11)
What treats colon cancer in combo with 5-FU by causing macrophages and T-cells to secrete cytokines to supress tumor growth?
levamisole
What treats melanoma?
IL-2
What treats acute promyelocytic leukemia and acne by allowing differentiation of promyelocytic cells into normal granulocytes?
tretinoin
