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Updated: Jul 30, 2026
Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm
Published on: December 22, 2016
Hematopoietic neoplasms in Prkar2a-deficient mice
Emmanouil Saloustros1, Paraskevi Salpea2, Chen-Feng Qi3
1Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN) & Pediatric Endocrinology Inter-institute Training Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. esaloustros@yahoo.gr.
Protein kinase A regulatory subunit RIIα deficiency predisposes mice to hematopoietic malignancies, specifically histiocytic sarcomas and diffuse large B cell lymphomas. This study reveals a previously unrecognized link between RIIα and these rare cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Protein kinase A (PKA) is crucial, with four regulatory subunits (RIα, RIβ, RIIα, RIIβ) and four catalytic subunits.
- Inactivating the RIα subunit (Prkar1a) causes embryonic lethality or neoplasms in mice.
- The tumor susceptibility of mice lacking RIIα (Prkar2a) or RIIβ (Prkar2b) subunits was unexamined.
Purpose of the Study:
- To investigate the role of PKA regulatory subunits RIIα and RIIβ in the development of hematopoietic malignancies.
- To determine if Prkar2a or Prkar2b gene inactivation influences tumor susceptibility in mice.
Main Methods:
- Cohorts of mice with varying Prkar1a, Prkar2a, and Prkar2b genotypes were monitored for hematologic malignancies.
- Tumor tissues were analyzed using immunohistochemistry and tumor-specific markers.
- Cell sorting and protein studies were conducted.
Main Results:
- Mice lacking Prkar2a (Prkar2a (-/-) and Prkar2a (+/-)) frequently developed hematopoietic neoplasms.
- Histiocytic sarcomas (HS) were the dominant tumor type, with rare diffuse large B cell lymphomas (DLBCL).
- Southern blot confirmed DLBCLs were clonal B cell neoplasms; other genotypes showed no significant tumor development.
Conclusions:
- Prkar2a deficiency significantly predisposes mice to developing hematopoietic malignancies in vivo.
- RIIα is identified as a potential factor in the development of HS and DLBCL.
- This finding may enhance the understanding of these rare neoplasms.
