Thrombopoiesis (Schalm 75) Flashcards
Progenitor cells committed to megakaryocyte lineage begin to express what four markers?
CD41 (GPIIb)
CD61 (GPIIIa)
CD42 (glycoprotein Ib)
Glycoprotein V
What is the function of PECAM-1? VCAM-1?
PECAM-1 may play a role in movement of megakaryocytes toward the vascular sinuses
VCAM-1 facilitates trans endothelial migration and proplatelet formation and release through the interaction of megakaryocytes with bone marrow endothelial cells
Name four transcription factors important in thrombopoiesis
GATA1, GATA2
Friend of GATA1, Friend leukemia integration 1, GA-binding protein
Core binding factors
Nuclear factor-erythroid 2
The core binding factors family contains what three DNA-binding proteins? What non-DNA binding protein
runt-related transcription factors (RUNX1), RUNX2, RUNX3
CBF-beta
What are three targets for the Nuclear Factor-erythroid 2 transcription factor?
Thromboxane synthase
B1 tubular
Rab27b
Caspase-12
CalDAG-GEFI
PINCH1
The lack of formation of a normal functioning mitosis spindle in megakaryocytes results in _____
Endomitosis (DNA division without cell division)
(Skipping anaphase, telophase, and cytokinesis)
What is the suggested purpose of the demarcation membrane system?
It may provide a membrane reservoir for the formation and extension of proplatelets
The DMS is a result of tubular invagination of the plasma membrane
How are granules and organelles transported into the developing proplatelet?
Along the microtubules. Movement is bidirectional
Two missense mutations in B1-tubulin have been described, causing ______
Macrothrombocytopenia
(Cavalier King Charles Spaniels)
(Cairn, Norfolk, and Jack Russell Terriers)
How much of the cytoplasm is consumed by proplatelet formation?
All of it. The nucleus is left behind to enter an apoptosis pathway.
The amino-terminal end of TPO is highly homologous with what other regulator?
Erythropoietin
TPO bindings results in activation of what signalling pathway?
JAK-STAT (Jak 2, STAT3, STAT5)
Where is TPO primarily produced?
Liver
(Lesser extend kidney and bone marrow)
TPO is produced through what two mechanisms?
Constitutively produced in steady state
Uptake of senescent platelets (depleted of sialic acid) by Ashwell-Morell receptor (AMR) on hepatocytes triggering TPO production
Severe thrombocytopenia results in TPO production by _____
Bone marrow stromal cells
Hepatic TPO production is enhanced by what inflammatory cytokine?
IL-6
TPO is bound to c-MPL on _____
Platelets and megakaryocytes
(Internalized and not available for stimulating thrombopoiesis above steady state)
What is the relationship of platelet size and number in different species?
Dogs and cats - platelet size and number are inversely proportional
Cows, goats, ponies - no correlation
Horses - platelet size and number are directly proportional
