Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 626, Issue -, Pages 51-57Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.08.017
Keywords
CLL; STYK1/NOK; Lymphadenectasis; B lymphocyte; B1 cells
Categories
Funding
- National Natural Science Foundation of China [81550030]
- CAMS Innovation Fund for Medical Sciences, China [2017-I2M-3-007]
- NIH, United States [01CA31534]
- Cancer Prevention Research Institute of Texas (CPRIT), United States [RP100612, RP120348]
- Marie Betzner Morrow Centennial Endowment, United States
- NIH/NIAAA, United States [U01 AA020926]
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This study reveals that STYK1/NOK can induce immunosuppressive B-CLL-like disease in transgenic mice, resulting in shorter lifespan. The phenotype of STYK1/NOK-induced B-CLL is heterogeneous, with lymphadenectasis and hepatomegaly and/or splenomegaly commonly observed. Additionally, STYK1/NOK-tg mice show reduced immune responses. The upregulation of STYK1/NOK is also observed in primary human B-CLL.
STYK1/NOK functions in a ligand independent and constitutive fashion to provoke tumor formation and to be up-regulated in many types of cancer cells. However, how STYK1/NOK functions at the whole animal level is completely unknown. Here, we found that STYK1/NOK-transgenic (tg) mice spontane-ously developed immunosuppressive B-CLL-like disease with generally shorter life spans. The phenotype of STYK1/NOK-induced B-CLL was typically heterogeneous, and most often, presented lymphadenectasis accompanied with hepatomegaly and/or splenomegaly. STYK1/NOK-tg mice also suffered reduced im-mune responses. The expanded CD5 thorn CD19 thorn (B1) lymphocyte pool was detected within peripheral lymphoid organs. Analysis on GEO profile revealed that expression of STYK1/NOK were significantly up -regulated in primary human B-CLL. Inoculation of blood cells from sick STYK1/NOK-tg mice into immune-deficient recipients recaptured the B1 malignant phenotype. Our study demonstrated that STYK1/NOK transgenic mouse may serve as a useful model system for the developments of novel diagnosis and treatment of B-CLL.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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