Hematopoiesis, Stem Cell Disorders

Question 1

two defining characteristics of stem cells

Answer 1

self renewal and differentiation

Question 2

totipotent

Answer 2

germ cells. capable of differentiating into anything

Question 3

pluripotent

Answer 3

has the ability to differentiate into multiple things

Question 4

what is the potency of human stem cells?

Answer 4

pluripotent

Question 5

example of totipotent cell?

Answer 5

morula

Question 6

normal stem cell division

Answer 6

1:1 balance, 1 self renewing daughter cell and 1 lineage specific daughter cell

Question 7

example of stem cell division with two differentiated cells

Answer 7

aplastic anemia

Question 8

example of stem cell division with two self renewing cells

Answer 8

leukemia

Question 9

HSC division

Answer 9

rare cells with rare divisions. numbers remain constant throughout life

Question 10

if stem cells don’t divide often, which cells have the tremendous replicative capacity?

Answer 10

lineage specific progenitor cells (i.e. myeloid/lymphoid progenitor cells)

Question 11

what do hematopoietic SCs divide into?

Answer 11

common lymphoid or myeloid progenitors

Question 12

what differentiates a progenitor cell from a stem cell?

Answer 12

progenitor cells divide a ton but don’t self renew

Question 13

what is the general environment that provides growth stimulation to HSCs?

Answer 13

marrow stroma

Question 14

two types of marrow stroma niches

Answer 14

endosteal and perivascular

Question 15

endosteal niche

Answer 15

promotes quiescent self-renewal

Question 16

perivascular niche

Answer 16

promotes active differentiation

Question 17

which cytokines regulate hematopoiesis?

Answer 17

interleukins (ILs) and colony stimulating factors (CSFs)

Question 18

GM-CSF (granulocyte/macrophage)

Answer 18

important CSFs for all cells of the myeloid lineage. stimulate differentiation, proliferation, and mobilization.

Question 19

cytotoxic injury to stem cells

Answer 19

chemotherapy and radiation kill rapidly dividing, undifferentiated cells. cytopenias are therefore expected side effects

Question 20

EPO (erythropoietin)

Answer 20

produced in the kidney and stimulates RBC production

Question 21

Effects of aging on HSCs

Answer 21

lower regenerative capacity, move more to perivascular niche, increased peripheral mobilization, myeloid skewed differentiation, increased self renewal capacity

Question 22

effects of aging on marrow

Answer 22

decreased cellularity (increased adiposity), impaired osteoclast/blast function, increased leukemias & anemias

Question 23

aplastic anemia

Answer 23

bone marrow failure due to suppression or disappearance of multi potent progenitor cells. Leads to cytopenias with any combo of anemia, thrombocytopenia, neutro/leukopenia

Question 24

causes of acquired aplastic anemia?

Answer 24

idiopathic (autoimmune, SC defects), cytotoxic injury (chemotherapy, radiation, drugs), viral (hep, CMV, EBV, varicella)

Question 25

treatment for aplastic anemia?

Answer 25

immunosuppressive therapy (IST), if IST fails, then HSC transplantation

Question 26

when would you treat aplastic anemia with HSC transplantation first?

Answer 26

if a pediatric patient has a matched sibling

Question 27

fanconi anemia

Answer 27

congenital stem cell defect in which there is a double stranded DNA repair defect. short stature, cancer predisposition, radial anomalies.

Question 28

dyskeratosis congenita

Answer 28

congential stem cell defect in which there is a telomerase defect leading to increased cell apoptosis, skin dyspigmentation, oral leukoplakia, hair/nail dystrophy. fast growing cells affected

Question 29

autologous transplantation

Answer 29

high dose chemotherapy followed by stem cell rescue from patients own HSCs. GM-CSF mobilizes HSCs into periphery, they are then removed and replaced after chemo. can only be used to treat non-stem cell problems

Question 30

allogeneic transplantation

Answer 30

non-self HSC donor. HLA matched. used to replace faulty HSCs

Question 31

GVHD

Answer 31

graft vs host disease. donor t cell attacks host tissue

Question 32

graft rejection

Answer 32

host t cell attacks donor HSCs