PO.TB05.02 · 肿瘤生物学
MIAC51 细胞在多种大鼠品系中诱导快速起病的白血病：一种新型且可重复的绿色白血病（Chloroleukemia）模型
MIAC51 cells induce rapid-onset leukemia across multiple rat strains: A novel and reproducible model of Chloroleukemia
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
美国癌症协会指出白血病是最常见的儿童癌症形式，近五分之一的儿童白血病病例为急性髓系白血病（AML）。风险分组分层和化疗方案的进展改善了儿童患者的临床结局，使 5 年生存率达到约 70%。鉴于多达 30% 的患者复发且其预期生存率大幅降低，白血病的治疗仍面临重大挑战。理解儿童白血病大多未知的病因的努力，已因动物建模而大大推进，动物模型可模拟生物学多系统受累和更准确的疾病状态。我们旨在利用大鼠绿色白血病细胞系 MIAC51 细胞，在有限的 AML 模型库中记录一种新的可行动物模型。多种品系的 7 日龄大鼠幼崽经腹腔注射 MIAC51 大鼠细胞，并与接受生理盐水的相应对照组进行比较。所有幼崽在注射后第 7 天和第 14 天均通过剪尾法采集 50 μL 血液。进行全血细胞计数（CBC）和分类染色以检测白血病的存在。在注射后第 14 天，所有受试品系：Wistar、Sprague Dawley、Long Evans、Brown Norway 和 Fischer 344，均以 100% 的成功率发生白血病。在外周血中发现绿色白血病原始细胞，经 Wright 染色和 CBC 证实提示 AML。本研究在此建立了一种使用 MIAC51 细胞的新型且可重复的幼鼠白血病模型，证明在所有受试品系中均可实现一致的植入和白血病转化。白血病状态的诱导经外周血染色中绿色白血病原始细胞的存在和 CBC 异常证实。该模型将通过提供一个在幼龄宿主中研究白血病发生和白血病病理生理学的平台，加速血液学科研成果的转化，并与儿童急性髓系白血病相关。对绿色白血病诱导机制基础的探究以及对该白血病模型的进一步遗传分析，将有助于界定其对人类儿童 AML 的忠实性，并确定其在下游临床前应用中的效用。
查看英文原文 English abstract
The American Cancer society states leukemia as the most prevalent form of pediatric cancer, nearly 1 in 5 cases of childhood leukemia are acute myeloid leukemia (AML). Advances in risk-group stratification, and chemotherapeutic regimens, have improved clinical outcomes for pediatric patients such that 5-year survival rates are at around 70%. Significant challenges remain in their treatment of leukemia, considering as many as 30% of patients relapse and the expected survival rate is drastically lower. Efforts to understand the mostly unknown etiology of childhood leukemia have been greatly improved by animal modeling which can simulate biological multi-system involvement and a more accurate disease state. We aim to document a new viable animal model in the limited repertoire of AML models using MIAC51 cells, a rat Chloroleukemia cell line. Multiple strains of rat pups, at 7 days old, were injected intraperitoneally with MIAC51 rat cells and compared to respective control groups who received saline solution. All pups had 50 µL of blood drawn at both 7- and 14-days post-injection via tail snip method. Complete blood count (CBC), and differential staining were performed to detect presence of leukemia. At 14 days post-injection, all breeds tested: Wistar, Sprague Dawley, Long Evans, Brown Norway, and Fischer 344, developed leukemia with 100% success rate. Chloroleukemia blasts were found in peripheral blood, indicative of AML as confirmed by Wright stain and CBC. Established here is a novel and reproducible young-rat leukemia model using MIAC51 cells, demonstrating consistent engraftment and leukemic transformation across all tested breeds. Induction of leukemic-state was confirmed by the presence of Chloroleukemia blasts in peripheral blood staining and CBC abnormalities. This model will accelerate translation of hematological science research by providing a platform for studying leukemogenesis, and leukemic pathophysiology in a young-host, with relevance to childhood acute myeloid leukemias. Inquiry into the mechanistic basis for Chloroleukemia induction, and further genetic analysis of the leukemia model will help define its fidelity to human pediatric AML and determine its utility in downstream pre-clinical application.
利益披露 Disclosure
J. Costoya, None..
J. J. Jimenez, None.