Hematopoietic neoplasms in Prkar2a-deficient miceReport as inadecuate

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Journal of Experimental and Clinical Cancer Research

, 34:143

First Online: 25 November 2015Received: 18 June 2015Accepted: 11 November 2015DOI: 10.1186-s13046-015-0257-z

Cite this article as: Saloustros, E., Salpea, P., Qi, CF. et al. J Exp Clin Cancer Res 2015 34: 143. doi:10.1186-s13046-015-0257-z


BackgroundProtein kinase A PKA is a holoenzyme that consists of a dimer of regulatory subunits and two inactive catalytic subunits that bind to the regulatory subunit dimer. Four regulatory subunits RIα, RIβ, RIIα, RIIβ and four catalytic subunits Cα, Cβ, Cγ, Prkx have been described in the human and mouse genomes. Previous studies showed that complete inactivation of the Prkar1a subunit coding for RIα in the germline leads to embryonic lethality, while Prkar1a–deficient mice are viable and develop schwannomas, thyroid, and bone neoplasms, and rarely lymphomas and sarcomas. Mice with inactivation of the Prkar2a and Prkar2b genes coding for RIIα and RIIβ, respectively are also viable but have not been studied for their susceptibility to any tumors.

MethodsCohorts of Prkar1a, Prkar2a, Prkar2a, Prkar2b and wild type WT mice have been observed between 5 and 25 months of age for the development of hematologic malignancies. Tissues were studied by immunohistochemistry; tumor-specific markers were also used as indicated. Cell sorting and protein studies were also performed.

ResultsBoth Prkar2a and Prkar2a mice frequently developed hematopoietic neoplasms dominated by histiocytic sarcomas HS with rare diffuse large B cell lymphomas DLBCL. Southern blot analysis confirmed that the tumors diagnosed histologically as DLBCL were clonal B cell neoplasms. Mice with other genotypes did not develop a significant number of similar neoplasms.

ConclusionsPrkar2a deficiency predisposes to hematopoietic malignancies in vivo. RIIα’s likely association with HS and DLBCL was hitherto unrecognized and may lead to better understanding of these rare neoplasms.

KeywordsProtein kinase A Histiocytic sarcoma Cyclic AMP Diffuse large B cell lymphoma Carney complex AbbreviationsPKAProtein Kinase A

WTWild Type

DLBCLDiffuse Large B Cell Lymphoma

CNCCarney Complex

HSHistiocytic Sarcoma


HandEHematoxylin and Eosin

MZLMarginal Zone Lymphoma

HRHistiocytic Rich

FACSFluorescence Activated Cell Sorting

BMBone Marrow

TCRT Cell Receptor

Emmanouil Saloustros and Paraskevi Salpea contributed equally to this work.

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Author: Emmanouil Saloustros - Paraskevi Salpea - Chen-Feng Qi - Lina A. Gugliotti - Kitman Tsang - Sisi Liu - Matthew F. Starost

Source: https://link.springer.com/

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