Related Experiment Video

Updated: Jun 27, 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

14.9K

Enhanced Molecular Response in Myeloproliferative Neoplasms with Complete JAK2V617F Inhibition

Hamza Celik1, Grant A Challen2

  • 1Incyte Research Institute, Wilmington, Delaware.

Cancer Discovery
|May 1, 2024
PubMed
Abstract

Insights

A new JAK2V617F mouse model shows these mutations require specific cells to survive. This suggests targeted therapies could potentially cure myeloproliferative neoplasms, even with other mutations present.

Area of Science:

  • Hematology
  • Genetics
  • Oncology

Background:

  • The JAK2V617F mutation is a key driver in myeloproliferative neoplasms (MPNs).
  • Understanding the cellular requirements for JAK2V617F-driven MPNs is crucial for developing effective treatments.

Purpose of the Study:

  • To develop and characterize a novel genetic mouse model with inducible and reversible JAK2V617F expression.
  • To investigate the role of specific cell populations in the survival and propagation of MPNs driven by JAK2V617F.

Main Methods:

  • Creation of a mouse model with JAK2V617F expression controlled by an inducible and reversible system at the endogenous locus.
  • Analysis of MPN development, progression, and cellular dependencies in the developed mouse model.

Main Results:

  • The study demonstrates that myeloproliferative neoplasm-initiating cells are essential for the survival of MPNs driven by the JAK2V617F mutation.
  • Inducible and reversible expression of JAK2V617F in the mouse model allowed for detailed investigation of its effects on hematopoietic stem and progenitor cells.

Conclusions:

  • JAK2V617F-driven MPNs absolutely require specific initiating cells for their survival.
  • The findings suggest that highly effective inhibitors targeting these essential cells could offer curative potential for MPN patients, even those with cooperating mutations.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

81
Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm08:12

Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm

Published on: December 22, 2016

11.9K

Related Concept Videos

Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
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...
8.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.1K