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August 11, 2016HaematologicaOpen Access

Revealing eltrombopags promotion of human megakaryopoiesis through AKT/ERK-dependent pathway activation

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Key result

Eltrombopag promoted human megakaryocyte differentiation and platelet production in a dose-dependent manner, achieving up to a 4-fold increase in proplatelet formation at 2000 ng/ml compared to thrombopoietin.

Why the study?

Does eltrombopag improve megakaryocyte differentiation and platelet production in human hematopoietic stem cells?

Population

Human cord blood-derived hematopoietic stem cells and adult peripheral blood progenitor cells from healthy…

Comparison

Eltrombopag cultured in vitro for 13 days vs 10 ng/ml recombinant human thrombopoietin as…

Design

Preclinical

Follow-up

13 days

Authors

CBChristian A. Di BuduoMCManuela CurraoAPAlessandro Pecci

Discussion

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Overview

May support investigation in thrombocytopenia; leaves open clinical translation pending in vivo human trials.

Structured PICO

Does eltrombopag improve megakaryocyte differentiation and platelet production in human hematopoietic stem cells?

P
Population
In vitro and ex vivo study utilizing human cord blood and peripheral blood-derived hematopoietic stem cells to evaluate the mechanisms of eltrombopag on megakaryopoiesis.
I
Intervention
Eltrombopag (50, 100, 200, 500 or 2000 ng/ml) cultured in vitro for 13 days
C
Comparator
10 ng/ml recombinant human thrombopoietin (rHuTPO) as standard control
O
Outcome
Megakaryocyte differentiation and proplatelet formationsurrogate

Main Result

p-value: p=<0.05

Eltrombopag promotes human megakaryocyte differentiation and platelet production in vitro through balanced activation of AKT and ERK1/2 pathways.

Limitations

  • Inability to use traditional in vivo animal models due to eltrombopag's selective activity only in humans and chimpanzees.
  • Further studies are required to ascertain whether the observed in vitro differences occur in vivo in patients.

Cite This Study

Buduo et al. (2016) studied Thrombocytopenia / Megakaryopoiesis. Eltrombopag vs. 10 ng/ml recombinant human thrombopoietin (rHuTPO) was evaluated on Megakaryocyte output and proplatelet formation (p=<0.05). Eltrombopag promoted human megakaryocyte differentiation and platelet production in a dose-dependent manner, achieving up to a 4-fold increase in proplatelet formation at 2000 ng/ml compared to thrombopoietin.

synapsesocial.com/papers/6a82e6fc57df60cfb510c672https://doi.org/10.3324/haematol.2016.146746
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Thrombopoietin Regulates Bcl-xL Gene Expression through Stat5 and Phosphatidylinositol 3-Kinase Activation Pathways2002 · 104 citations
  2. 2Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes2012 · 39 citations
  3. 3Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation2012 · 167 citations
  4. 4Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia2012 · 553 citations
  5. 5Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells2014 · 88 citations