意大利应用科学与智能系统研究所Pasquale Memmolo团队研究了从基因型到表型：全断层流式细胞术解码母细胞突变。2025年7月2日出版的《光：科学与应用》杂志发表了这项成果。

急性髓系白血病（AML）母细胞杯状核形态改变与核蛋白1（NPM1）突变广泛相关。NPM1突变的AML已被公认为髓系肿瘤中的一个独特实体，但缺乏彻底建立的形态学分析工具仍然是一个显著的差距。全息断层扫描（HT）可以提供一种无标记的解决方案，用于根据核折射率（RI）的体积变化定量评估核的3D形状。然而，传统的HT方法分析2D层中的贴壁细胞，由于缺少锥体伪影，导致非各向同性重建。

研究组首次表明，全断层流式细胞术（HTFC）实现了悬浮AML细胞中核体积形状的定量特异性和精确捕获。为了在流动AML细胞的无标记RI断层图像中检索核特异性，他们设想并在一个真实的临床案例中演示了一种分割3D凹形核的新策略。这种方法意味着，通过HTFC，在AML核的异常形态特征和NPM1突变之间建立了一种尚未探索的具有挑战性的联系，从而证明了核的“表型”和“基因型”之间的相关性。

研究组对NPM1野生型和NPM1突变的母细胞进行了总体水平的统计表征，以辨别它们复杂的形态和生物物理差异。该研究结果表明，通过HTFC表征NPM1相关AML细胞中的杯状核可能会增强这些肿瘤的诊断方法。此外，还整合了虚拟现实，在真实的3D环境中提供AML细胞形态变化的沉浸式成果。

附：英文原文

Title: From genotype to phenotype: decoding mutations in blasts by holo-tomographic flow cytometry

Author: Pirone, Daniele, Di Natale, Concetta, Di Summa, Maria, Mosca, Nicola, Giugliano, Giusy, Schiavo, Michela, Florio, Daniele, Marasco, Daniela, Maffettone, Pier Luca, Miccio, Lisa, Memmolo, Pasquale, Ferraro, Pietro

Issue&Volume: 2025-07-02

Abstract: Cup-like nuclear morphological alterations in acute myeloid leukemia (AML) blasts have been widely correlated with Nucleophosmin 1 (NPM1) mutations. NPM1-mutated AML has earned recognition as a distinct entity among myeloid tumors, but the absence of a thoroughly established tool for its morphological analysis remains a notable gap. Holographic tomography (HT) can offer a label-free solution for quantitatively assessing the 3D shape of the nucleus based on the volumetric variations of its refractive indices (RIs). However, traditional HT methods analyze adherent cells in a 2D layer, leading to non-isotropic reconstructions due to missing cone artifacts. Here we show for the first time that holo-tomographic flow cytometry (HTFC) achieves quantitative specificity and precise capture of the nucleus volumetric shape in AML cells in suspension. To retrieve nucleus specificity in label-free RI tomograms of flowing AML cells, we conceive and demonstrate in a real-world clinical case a novel strategy for segmenting 3D concave nuclei. This method implies that the correlation between the “phenotype” and “genotype” of nuclei is demonstrated through HTFC by creating a challenging link not yet explored between the aberrant morphological features of AML nuclei and NPM1 mutations. We conduct an ensemble-level statistical characterization of NPM1-wild type and NPM1-mutated blasts to discern their complex morphological and biophysical variances. Our findings suggest that characterizing cup-like nuclei in NPM1-related AML cells by HTFC may enhance the diagnostic approach for these tumors. Furthermore, we integrate virtual reality to provide an immersive fruition of morphological changes in AML cells within a true 3D environment.

DOI: 10.1038/s41377-025-01913-y

Source: https://www.nature.com/articles/s41377-025-01913-y