Related Experiment Video

Updated: Jun 19, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Dual CDK2 and CDK4/6 inhibition suppresses Rb/E2F signaling and enhances anti-leukemic activity in acute myeloid

Ellen Weisberg1, Basudev Chowdhury2, Swati Garg3

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA. ellen_weisberg@dfci.harvard.edu.

Haematologica
|June 18, 2026
PubMed

Insights

Cyclin-dependent kinase 6 (CDK6) inhibition shows promise in sensitizing acute leukemia cells to therapies. Combining CDK2 and CDK4/6 inhibitors demonstrates synergistic effects, offering a novel therapeutic strategy for acute leukemias.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cyclin-dependent kinase 6 (CDK6) is crucial in cell cycle regulation and acute leukemia development.
  • CDK4/6 inhibitors showed limited efficacy as monotherapy in acute leukemias, despite preclinical promise.
  • Combinations of CDK4/6 inhibitors with chemotherapy have shown clinical efficacy in pediatric acute leukemia.

Purpose of the Study:

  • To evaluate CDK6 inhibition's potential to sensitize acute myeloid leukemia (AML) cells to existing and novel therapies.
  • To explore the synergistic effects of combining CDK2 and CDK4/6 inhibitors in acute leukemia models.
  • To identify novel therapeutic strategies for acute leukemias involving CDK inhibitors.

Main Methods:

  • Investigated the efficacy of tegtociclib (CDK2 inhibitor) in combination with CDK4/6 inhibitors.
  • Assessed the synergistic effects of combined CDK inhibitors on acute leukemia cells.
  • Analyzed the impact on the Rb/E2F axis and cell cycle progression.

Main Results:

  • Tegtociclib potentiated the effects of CDK4/6 inhibitors against acute leukemia cells.
  • Synergistic effects were observed between CDK2 and CDK4/6 inhibitors in acute leukemia, similar to breast cancer findings.
  • Synergy correlated with suppression of the Rb/E2F axis and cell cycle inhibition.

Conclusions:

  • Combining CDK2 and CDK4/6 inhibitors represents a novel and effective strategy for acute leukemias.
  • The underlying mechanisms of synergy are conserved across different cancer types, including breast cancer and AML.
  • This approach warrants further investigation for other malignancies dependent on these cyclin-dependent kinases.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation09:09

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation

Published on: November 10, 2017

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...