Establishment of CD34 + hematopoietic stem cell-derived xenograft model of hyperleukocytic acute myeloid leukemia.

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-03-18 DOI:10.1186/s12885-025-13907-5

Yanxia Jin, Yuxing Liang, Balu Wu, Sanyun Wu, Xiaoyan Liu, Fuling Zhou

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引用次数: 0

Abstract

Background: Hyperleukocytic acute myeloid leukemia (HLL) is marked by high early mortality and presents significant therapeutic challenges. Research on HLL is still in its infancy, and comprehensive development of patient-derived xenograft (PDX) models, especially CD34 + hematopoietic stem cell-derived models, remains limited.

Methods: We evaluated the establishment of the HLL model through blood examinations, smear analysis, bone marrow biopsy, flow cytometry, and mutation analysis. Correlation between survival times in mice and patients was assessed using linear regression.

Results: In the HLL PDX mouse model, leukocyte counts could reach up to 37.35^10⁹/L, and immunophenotyping revealed the presence of hCD45+, hCD15+, and hCD33 + cells in both peripheral blood (PB) and bone marrow (BM) following inoculation with PB-derived cells for the establishment of the HLL PDX model. Similar results were observed with cells derived from the patient's BM. In the CD34 + hematopoietic stem cell-derived xenograft model, extensive infiltration of CD34 + cells into the BM, liver, and spleen was observed. Additionally, human WT1 and NRAS mutations were identified in the liver, spleen, and BM of the mice. A comparative analysis of multiple experiments revealed that shorter survival times were observed in mice receiving a higher irradiation dose of 2.5 Gy and a greater number of cells derived from PB. Additionally, shorter survival times were observed in model mice injected with cells carrying NRAS, DNMT3A, FLT3, or NPM1 gene mutations. Correlation analysis indicated that the survival times of the mice were significantly associated with the survival status of the patients.

Conclusions: We successfully established a CD34 + hematopoietic stem cell-derived xenograft model of HLL, providing a valuable tool for mechanistic research, drug screening, individualized therapy, and precision medicine.

Trial registration: Not application.

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背景：高白细胞急性髓性白血病（HLL）的特点是早期死亡率高，给治疗带来了巨大挑战。关于 HLL 的研究仍处于起步阶段，患者衍生异种移植（PDX）模型，尤其是 CD34 + 造血干细胞衍生模型的全面发展仍然有限：方法：我们通过血液检查、涂片分析、骨髓活检、流式细胞术和突变分析来评估 HLL 模型的建立。使用线性回归评估了小鼠和患者存活时间之间的相关性：结果：在HLL PDX小鼠模型中，白细胞计数可高达37.35^10⁹/L，免疫分型显示，接种PB衍生细胞以建立HLL PDX模型后，外周血（PB）和骨髓（BM）中均存在hCD45+、hCD15+和hCD33+细胞。从患者骨髓中提取的细胞也观察到了类似的结果。在 CD34 + 造血干细胞衍生的异种移植模型中，观察到 CD34 + 细胞广泛浸润到骨髓、肝脏和脾脏。此外，在小鼠的肝脏、脾脏和BM中还发现了人类WT1和NRAS突变。对多项实验的比较分析表明，接受 2.5 Gy 较高照射剂量和较多 PB 细胞的小鼠存活时间较短。此外，在注射了携带 NRAS、DNMT3A、FLT3 或 NPM1 基因突变的细胞的模型小鼠中也观察到较短的存活时间。相关分析表明，小鼠的存活时间与患者的存活状况有显著相关性：我们成功建立了一种 CD34 + 造血干细胞衍生的 HLL 异种移植模型，为机理研究、药物筛选、个体化治疗和精准医疗提供了有价值的工具：未申请。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.