Ali Haadi, Reynolds Sam, Wilcox Sabrina, Chipalkatti Naina, Ahmed Asra
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.
Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI, United States of America.
Ann Hematol. 2024 Dec;103(12):5123-5144. doi: 10.1007/s00277-024-05928-0. Epub 2024 Aug 27.
We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94 K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.
我们旨在研究相对单核细胞增多症与肺朗格汉斯细胞组织细胞增多症复发之间的关联。收集了86例经组织病理学诊断为朗格汉斯细胞组织细胞增多症患者在20年期间的临床、实验室、影像学和治疗数据。收集了诸如生物学性别、诊断时年龄、诊断时间、分子诊断数据和影像学等参数。主要通过影像学评估治疗反应，将RECIST 1.1标准应用于MRI或CT扫描，并将PERCIST用于系列PET成像。研究人员还在各个时间点评估外周血绝对单核细胞计数，包括初始诊断时和最近可得的值。虽然最早评估时间点与最新值之间的外周血绝对单核细胞计数没有差异，但进展时的平均值（0.94 K/µL）显著高于重新开始治疗后的平均值（0.31，p = 0.000794）。我们观察到LCH疾病进展时的相对单核细胞增多症可能与疾病进展时循环LCH增加或单核细胞产生增加有关，后者随后分化为参与MHC Ⅰ类上调的成熟树突状细胞。这种趋势在由组织创伤和环境因素刺激引起的肺LCH中尤为明显。我们研究中观察到的现象与其他非LCH队列相似，特别是我们自己团队发表的关于Rosai Dorfman病和Erdheim Chester病患者的研究结果。为了进一步阐明LCH的分子基础并探索这种单核细胞趋势的病因，正在进行扩展的综合基因组-转录组测序分析，以评估LCH的分子特征并最终阐明这种单核细胞趋势的起源。这些研究有望为LCH潜在的分子机制提供宝贵的见解，特别是与单核细胞信号传导和分化相关的机制。
