JAK2突变通过增强其致癌性，在急性淋巴细胞白血病（ALL）的发病机制中发挥着临床重要作用。该研究旨在表征巴基斯坦起源的 ALL 队列中 JAK2 突变的分子病理学和计算特征。93 名患者参加了当前的研究。通过流式细胞术和骨髓抽吸物/血液的核型分析证实了疾病诊断。为了识别致病基因变异并评估其潜在影响，JAK2 基因分别进行了直接测序、预测计算和计算机结构分析。在 10 名 (11%) 患者中检测到 JAK2 突变。所有突变均为错义，其中 1 个突变为移码。大多数突变表现出与野生型相似的模式，但 p.N673H p.V674L p.C675W (AAD699)、p.V674F (AA​​D704) 和 p.V674L (AAD705) 表现出统计学上显着的稳定性损失。三重突变显示出整体和局部的稳定性降低。研究队列中 JAK2 的基因缺陷模式显示出正确折叠行为的破坏，这从旋转值的增加中可以明显看出，从而导致假设这些突变可能导致 JAK2 的结构改变导致疾病进展的蛋白质。© 作者 2024。由牛津大学出版社代表美国临床病理学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限均可通过我们网站文章页面上的“权限”链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

JAK2 mutation plays a clinically significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) by enhancing its oncogenicity. The study aimed to characterize the molecular pathology and computational profile of the JAK2 mutation in an ALL cohort of Pakistani origin.Ninety-three patients were enrolled in the current study. The disease diagnosis was confirmed via flow cytometry and karyotyping of bone marrow aspirate/blood. For the identification of causative gene variations and assessment of their potential impact, the JAK2 gene underwent direct sequencing and predictive computational and in silico structural analysis, respectively.JAK2 mutations were detected in 10 (11%) patients. All mutations were missense with 1 being frameshift. Most mutations showed a similar pattern to the wild type but p.N673H+p.V674L+p.C675W (AAD699), p.V674F (AAD704), and p.V674L (AAD705) exhibited statistically significant stability loss. The triple mutation displayed reduced stability both globally and locally.The pattern of gene defects in JAK2 in the studied cohort showed a disruption in proper folding behavior, evident from increased gyration values, resulting in the hypothesis that these mutations may cause structural alterations in the JAK2 protein that lead to disease progression.© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.