The malignant transformation potential of the oncogene STYK1/NOK at early lymphocyte development in transgenic mice

Yin Yang; Li Liu; Haley O Tucker

doi:10.1016/j.bbrep.2024.101709

The malignant transformation potential of the oncogene STYK1/NOK at early lymphocyte development in transgenic mice

Biochem Biophys Rep. 2024 Apr 12:38:101709. doi: 10.1016/j.bbrep.2024.101709. eCollection 2024 Jul.

Authors

Yin Yang¹, Li Liu¹, Haley O Tucker²

Affiliations

¹ Department of Pathogen Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
² Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, 1 University Station A5000, Austin, TX, 78712, USA.

Abstract

B-cell Chronic Lymphocytic Leukemia (B-CLL) is a malignancy caused by the clonal expansion of mature B lymphocytes bearing a CD5⁺CD19⁺ (B1) phenotype. However, the origin of B-CLL remains controversial. We showed previously that STYK1/NOK transgenic mice develop a CLL-like disease. Using this model system in this study, we attempt to define the stage of CLL initiation. Here, we show that the phenotype of STYK1/NOK-induced B-CLL is heterogeneous. The expanded B1 lymphocyte pool was detected within peripheral lymphoid organs and was frequently associated with the expansions of memory B cells. Despite this immunophenotypic heterogeneity, suppression of B cell development at an early stage consistently occurred within the bone marrow (BM) of STYK1/NOK-tg mice. Overall, we suggest that enforced expression of STYK1/NOK in transgenic mice might significantly predispose BM hematopoietic stem cells (HSCs) towards the development of B-CLL.

Keywords: B lymphocyte; B1 cells; CLL; HSC; Lymphadenectasis; STYK1/NOK.