AML is a highly aggressive and heterogeneous form of hematological cancer. Proteomics-based stratification of patients into more refined subgroups may contribute to a more precise characterization of the patient-derived AML cells. Here, we reanalyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) generated proteomic and phosphoproteomic data from 26 FAB-M4/M5 patients. The patients achieved complete hematological remission after induction therapy. Twelve of them later developed chemoresistant relapse (RELAPSE), and 14 patients were relapse-free (REL_FREE) long-term survivors. We considered not only the RELAPSE and REL_FREE characteristics but also integrated the French-American-British (FAB) classification, along with considering the presence of nucleophosmin 1 (NPM1) mutation and cytogenetically normal AML. We found a significant number of differentially enriched proteins (911) and phosphoproteins (257) between the various FAB subtypes in RELAPSE patients. Patients with the myeloblastic M1/M2 subtype showed higher levels of RNA processing-related routes and lower levels of signaling related to terms like translation and degranulation when compared with the M4/M5 subtype. Moreover, we found that a high abundance of proteins associated with mitochondrial translation and oxidative phosphorylation, particularly observed in the RELAPSE M4/M5NPM1mutated subgroup, distinguishes relapsing from non-relapsing AML patient cells with the FAB subtype M4/M5. Thus, the discovery of subtype-specific biomarkers through proteomic profiling may complement the existing classification system for AML and potentially aid in selecting personalized treatment strategies for individual patients.
急性髓系白血病（AML）是一种高度侵袭性且异质性强的血液系统恶性肿瘤。基于蛋白质组学将患者划分为更精细的亚组，有助于更精确地鉴定患者来源的AML细胞特征。本研究重新分析了26例FAB-M4/M5型患者的液相色谱-串联质谱（LC-MS/MS）蛋白质组学及磷酸化蛋白质组学数据。所有患者经诱导治疗后均达到完全血液学缓解，其中12例后续发生化疗耐药性复发（RELAPSE），14例为长期无复发生存者（REL_FREE）。我们在分析中不仅纳入复发与无复发特征，同时整合法美英（FAB）分型标准，并考虑NPM1基因突变及细胞遗传学正常AML的情况。研究发现，在复发患者的不同FAB亚型间存在大量差异富集的蛋白质（911种）和磷酸化蛋白质（257种）。与原粒细胞M4/M5亚型相比，原始细胞M1/M2亚型患者显示出更高水平的RNA加工相关通路活性，以及较低水平的翻译和脱颗粒相关信号通路。此外，我们发现线粒体翻译与氧化磷酸化相关蛋白的高表达（尤其在复发M4/M5NPM1突变亚组中显著）能够区分FAB-M4/M5亚型中复发与非复发AML患者细胞。因此，通过蛋白质组学分析发现亚型特异性生物标志物，可补充现有AML分型体系，并有望为个体化治疗策略的选择提供依据。
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