摘要:mCG-PML-RARα小鼠模型的白血病潜伏期受性别和肥胖的影响

John W R Kincaid, Annie E. Hill-Baskin, N. Berger
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引用次数: 0

摘要

据报道,人类白血病在发病率和行为上都表现出性别二态性。然而,很少在动物模型中进行这一观察的研究。我们使用C57BL/6J小鼠,通过基因工程在小鼠组织蛋白酶G (mCG)位点含有PML-RARA融合基因,作为急性早幼粒细胞白血病(APL)的模型(b6 .mCG- PML-RARA α),研究性别和饮食变化对疾病潜伏期的影响。30日龄时,对照(WT)和突变(mCG+/PR)小鼠按性别分开,分别饲喂高脂(HF)[57%椰子油脂肪]或低脂(LF)[10%椰子油脂肪]日粮。小鼠连续采血,当外周血出现粒细胞升高(WBC >20 K/μL)、贫血(Hb 425 d)等白血病发展迹象时处死。相比之下,饲喂LF的雄性mCG+/PR小鼠在360日龄时MLFS减少,潜伏期差异为65天,从而显示APL外观的性别二态性。HF饮食加速了雌性(MLFS = 277日龄)和雄性mCG+/PR小鼠(MLFS = 277日龄)APL的出现,其潜伏期也有65天的差异。由此可见,HF饮食使mCG+/PR小鼠APL的出现在雄性小鼠和雌性小鼠中分别提前了148天和148天。无论是HF还是LF饮食,WT小鼠都没有白血病发展的迹象。无论是HF还是LF饮食,WT小鼠均未观察到脾肿大。因此,尽管HF饮食和肥胖加速了B6患者APL的发病。mCG-PML-RARα小鼠的性别二态性仍然存在,在HF和LF饮食条件下,雌性小鼠比雄性小鼠表现出更长的潜伏期。总之,我们的研究提供了一个强大的小鼠模型来研究性别影响白血病潜伏期的机制,并证明肥胖在不影响性别二态性的情况下加速了白血病的发展。引文格式:John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger。mCG-PML-RARα小鼠模型的白血病潜伏期受性别和肥胖的影响[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2584。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract 2584: Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity
Human leukemias have been reported to show sexual dimorphism in both incidence and behavior. However, few studies of this observation have been conducted in animal models. We used the C57BL/6J mouse, genetically engineered to contain the PML-RARA fusion gene at the mouse cathepsin G (mCG) locus, as a model (B6.mCG-PML-RARα) of acute promyelocytic leukemia (APL) to interrogate the impact of sex and diet variation on disease latency as measured by leukemia-free survival. At 30 days of age, control (WT) and mutant (mCG+/PR) mice were separated by sex and provided with high fat (HF) [57% coconut oil fat] or low fat (LF) [10% coconut oil fat] diets. Mice were followed with serial blood collections and sacrificed when peripheral blood revealed signs of leukemia development including elevated granulocytes (WBC >20 K/μL), anemia (Hb 425 days was observed. In contrast, male mCG+/PR mice fed LF diets showed a reduced MLFS of 360 days of age, indicating a difference in latency of 65 days, thereby demonstrating sexual dimorphism in the appearance of APL. HF diet accelerated the appearance of APL in both female (MLFS = 277 days of age) and male mCG+/PR mice (MLFS = 277 days of age), which also displayed a difference in latency of 65 days. Thus, HF diet accelerated appearance of APL by 148 days in male and 148 days in female mCG+/PR mice. There were no signs of leukemia development in WT mice on either HF or LF diets. There was no splenomegaly observed in WT mice on either HF or LF diets. Thus, although HF diet and obesity accelerate the onset of APL in B6.mCG-PML-RARα mice, sexual dimorphism remains, with females showing extended latency compared to males under conditions of both HF and LF diets. Overall, our studies provide a robust mouse model to study the mechanisms by which sex impacts leukemia latency, as well as demonstrate that obesity accelerates leukemia development without affecting sexual dimorphism. Citation Format: John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger. Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2584.
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