Related Experiment Video

Updated: May 10, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

AKT is a therapeutic target in myeloproliferative neoplasms

I Khan1, Z Huang, Q Wen

  • 1Division of Hematology, Northwestern University, Chicago, IL, USA.

Leukemia
|June 11, 2013
PubMed

Insights

The AKT inhibitor MK-2206 shows promise for treating myeloproliferative neoplasms (MPNs). It effectively suppresses cancer cell growth, synergizes with existing therapies, and alleviates disease symptoms in preclinical models.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Most BCR-ABL1-negative myeloproliferative neoplasms (MPNs) involve JAK2 or MPL mutations, leading to overactive JAK/STAT, PI3K, and ERK pathways.
  • Current JAK inhibitors are insufficient for clonal suppression in MPNs and can cause hematologic toxicities.

Purpose of the Study:

  • To investigate the efficacy of the AKT inhibitor MK-2206 as a therapeutic strategy for MPNs.
  • To determine if MK-2206 can synergize with ruxolitinib and impact disease progression in preclinical MPN models.

Main Methods:

  • Assessed the effect of MK-2206 on JAK2V617F- or MPLW515L-expressing cells.
  • Evaluated the synergistic effect of MK-2206 with ruxolitinib in JAK2V617F-mutant cells.
  • Examined MK-2206's impact on hematopoietic progenitor cells from primary myelofibrosis patients and in a mouse model of MPLW515L-induced MPN.

Main Results:

  • MK-2206 inhibited AKT signaling and affected the growth of cells with JAK2V617F or MPLW515L mutations.
  • MK-2206 demonstrated synergy with ruxolitinib in suppressing JAK2V617F-mutant cells.
  • MK-2206 suppressed colony formation in primary myelofibrosis patients and reduced MPN-related symptoms in a mouse model.

Conclusions:

  • The PI3K/AKT pathway is a viable therapeutic target in MPNs.
  • MK-2206 shows potential as a treatment for MPNs, both as a monotherapy and in combination with other agents.

Related Concept Videos

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 specific...
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 specific...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...