Related Experiment Video

Updated: Oct 14, 2025

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.0K

Mutated JAK2 signal transduction in human induced pluripotent stem cell (iPSC)-derived megakaryocytes

Jaturawat Pawinwongchai1, Panchalee Jangprasert2, Nungruthai Nilsri3

  • 1Faculty of Medical Technology, Rangsit University, Pathum Thani, Thailand.

Platelets
|November 9, 2021
PubMed

Insights

Janus kinase 2 (JAK2) mutations drive polycythemia vera and essential thrombocythemia. This study used induced pluripotent stem cells to show JAK2V617F promotes megakaryocytes, while JAK2exon12 does not, offering insights into disease mechanisms and new treatments.

Area of Science:

  • Hematology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Janus kinase 2 (JAK2) gene mutations are primary drivers of myeloproliferative neoplasms like polycythemia vera (PV) and essential thrombocythemia (ET).
  • The distinct disease phenotypes arising from a single altered JAK2 gene remain incompletely understood.
  • Novel therapeutic strategies targeting mutated JAK2 are critically needed.

Purpose of the Study:

  • To investigate the distinct effects of JAK2V617F and JAK2exon12 mutations on megakaryocyte differentiation using an induced pluripotent stem cell (iPSC) model.
  • To compare the signaling pathways activated by different JAK2 mutations.
  • To evaluate the efficacy of interferon alpha and arsenic trioxide in targeting mutated JAK2 signaling.

Main Methods:

  • Human iPSCs were engineered to express wild-type JAK2 (JAK2WT), JAK2V617F, or JAK2exon12 under a doxycycline-inducible system.
  • Modified iPSCs were differentiated into megakaryocytes with or without doxycycline induction to isolate the effects of mutated JAK2.
  • Capillary Western analysis was used to assess JAK2 phosphorylation and downstream signaling pathways (STAT3, STAT5, AKT).

Main Results:

  • JAK2V617F expression significantly increased megakaryocyte numbers, consistent with the ET phenotype, whereas JAK2exon12 expression did not enhance megakaryopoiesis.
  • JAK2V617F induced higher JAK2 phosphorylation and increased STAT3, STAT5, and AKT activation, unlike JAK2WT and JAK2exon12.
  • Interferon alpha and/or arsenic trioxide inhibited megakaryocyte proliferation and reduced signaling in mutant JAK2-expressing iPSCs.

Conclusions:

  • JAK2V617F expression in iPSCs drives megakaryopoiesis with a distinct signaling profile compared to JAK2exon12.
  • Interferon alpha and arsenic trioxide preferentially suppress mutated JAK2 signaling over wild-type.
  • This iPSC model serves as a valuable platform for studying myeloproliferative neoplasm mechanisms and screening novel therapies.
Keywords:
InterferoniPSCsmegakaryocytesmyeloproliferative neoplasmssignal transduction

More Related Videos

Isolation of Mouse Megakaryocyte Progenitors10:30

Isolation of Mouse Megakaryocyte Progenitors

Published on: May 20, 2021

6.9K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

334

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.5K
iPS Cell Differentiation01:22

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.8K