Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

Catherine M Sawai | Jacquelyn Freund | Philmo Oh | Delphine Ndiaye-Lobry | Jamieson C Bretz | Alexandros Strikoudis | Lali Genesca | Thomas Trimarchi | Michelle A Kelliher | Marcus Clark | Jean Soulier | Selina Chen-Kiang | Iannis Aifantis
Cancer cell | 2012

D-type cyclins form complexes with cyclin-dependent kinases (CDK4/6) and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27(Kip1) and retinoblastoma tumor suppressor (Rb) is sufficient to rescue the development of Ccnd3(-/-) thymocytes. Furthermore, we show that a small molecule targeting the kinase function of cyclin D3:CDK4/6 inhibits both cell cycle entry in human T cell acute lymphoblastic leukemia (T-ALL) and disease progression in animal models of T-ALL. These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor.

Pubmed ID: 23079656

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087
  • Agency: NCI NIH HHS, United States
    Id: R01CA133379
  • Agency: NCI NIH HHS, United States
    Id: R01 CA149655
  • Agency: NCI NIH HHS, United States
    Id: R01 CA105129
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM088847
  • Agency: NCI NIH HHS, United States
    Id: R21 CA141399
  • Agency: NCI NIH HHS, United States
    Id: R01CA149655
  • Agency: NCI NIH HHS, United States
    Id: R01CA105129
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088847
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087-30
  • Agency: NCI NIH HHS, United States
    Id: 5 P30CA16087-31
  • Agency: NCI NIH HHS, United States
    Id: R01 CA133379
  • Agency: NCI NIH HHS, United States
    Id: R01 CA096899
  • Agency: NCI NIH HHS, United States
    Id: 5P30CA16087-31
  • Agency: NCI NIH HHS, United States
    Id: R21CA141399

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

View all literature mentions

Gene Expression Omnibus (GEO) (tool)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

View all literature mentions