Establishment of a chronic lymphocytic leukemia mouse model via adoptive transfer of Eμ-TCL1 transgenic splenocytes
10.3760/cma.j.cn121090-20241120-00461
- VernacularTitle:基于Eμ-TCL1转基因小鼠建立慢性淋巴细胞白血病小鼠模型
- Author:
Manxu ZHANG
1
;
Sha GUO
;
Abudukelimu NADIYA·
;
Alimu XIERENGULI·
;
Rui ZHANG
;
Xuejiao ZENG
;
Linyi ZHANG
;
Ranran ZHANG
;
Jianhua QU
Author Information
1. 新疆医科大学第一附属医院血液病中心，乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
Leukemia, lymphocytic, chronic, B-cell;
Models, animal;
CD5;
CD19
- From:
Chinese Journal of Hematology
2025;46(5):445-452
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To generate a chronic lymphocytic leukemia (CLL) mouse model with intact immune competence and short latency by adoptively transferring (AT) splenocytes from immunoglobulin heavy-chain enhancer-driven T-cell leukemia/lymphoma 1 (Eμ-TCL1) transgenic donors into wild-type (WT) recipients.Methods:Specific pathogen-free C57BL/6J WT mice and H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were utilized. The H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice were generated using CRISPR/Cas9 technology, and their genotypes were confirmed by PCR. Experimental animals were randomly divided into an adoptive transfer (AT) group and a WT control group ( n=10 per group). Mice in the AT group received an intraperitoneal injection of splenocytes from H11-Eμ-VH-TCL1-β-globin-PolyA knock-in mice. The weight and general condition of the mice were monitored. Mice were euthanized by cervical dislocation at 9 weeks post-transplantation. The CLL model was validated using key indicators, including pathological manifestations, changes in peripheral blood leukocyte counts, and immunophenotype. Results:AT group mice exhibited significantly increased spleen weight [ (0.92±0.16) g vs (0.06±0.01) g in WT group, P<0.05] and liver weight [ (2.11±0.56) g vs (1.42±0.13) g in WT group, P=0.006], indicative of marked splenomegaly and hepatomegaly. The peripheral blood leukocyte count was significantly higher in the AT group [ (124.33±8.74) ×10 9/L] compared to the WT group [ (5.55±1.67) ×10 9/L] ( P=0.002). Similarly, the percentage of peripheral blood B lymphocytes was markedly increased in the AT group versus the WT group [ (69.13±6.88) % vs (39.78±5.94) %, P<0.05]. Histopathological examination revealed CLL manifestations in the spleen, lymph nodes, and bone marrow of AT group mice, with significant lymphocytic infiltration observed in the liver, lung, and kidney tissues. Flow cytometry analysis showed that the percentages of CD19 +CD5 + B lymphocytes among total lymphocytes in peripheral blood, bone marrow, and spleen of the AT group were (61.37±9.92) %, (28.61± 7.08) %, and (86.03±5.78) %, respectively. These were significantly higher (all P<0.05) than in the WT group [ (4.51±1.32) %, (5.58±1.46) %, and (14.33±3.20) %]. Furthermore, these CLL-like cells in the AT group were positive for CD43 and CD200, but showed lower expression of CD20, CD22, and CD79b compared to WT B cells. Conclusion:Adoptive transfer of splenocytes from Eμ-TCL1 transgenic mice successfully established a CLL mouse model with a relatively short latency period. This model represents a valuable preclinical tool for investigating CLL and related pathologies.
