迄今为止，尚未对 ASXL1 突变骨髓疾病患者进行大规模基因组分析。我们回顾了 6043 名成年人的全面基因组分析结果，以通过 ASXL1 突变状态来表征临床病理特征和共突变模式。 ASXL1 突变发生在 1414 名患者 (23%) 中。突变共现测试显示 ASXL1 和 9 个基因（SRSF2、U2AF1、RUNX1、SETBP1、EZH2、STAG2、CUX1、CSF3R、CBL）的突变之间存在很强的共现性（p< 0.01）。对具有这些共突变的患者的进一步分析产生了一些新的发现。共突变模式支持 ASXL1/SF3B1 共突变可能在生物学上不同于 ASXL1/非 SF3B1 剪接体共突变。在 AML 中，ASXL1/SRSF2 共突变患者经常携带 STAG2 突变 (42%)，这取决于 ASXL1 和 SRSF2 突变的存在 (p<0.05)。 STAG2 和 SETBP1 突变也只出现在 ASXL1/SRSF2 共突变患者中，并且与不同的慢性骨髓表型相关。我们的研究结果支持某些多突变基因型可能与 ASXL1 突变骨髓疾病具有生物学相关性。

A large-scale genomic analysis of patients with ASXL1-mutated myeloid disease has not been performed to date. We reviewed comprehensive genomic profiling results from 6043 adults to characterize clinicopathologic features and co-mutation patterns by ASXL1 mutation status. ASXL1 mutations occurred in 1414 patients (23%). Mutation co-occurrence testing revealed strong co-occurrence (p < 0.01) between mutations in ASXL1 and nine genes (SRSF2, U2AF1, RUNX1, SETBP1, EZH2, STAG2, CUX1, CSF3R, CBL). Further analysis of patients with these co-mutations yielded several novel findings. Co-mutation patterns supported that ASXL1/SF3B1 co-mutation may be biologically distinct from ASXL1/non-SF3B1 spliceosome co-mutation. In AML, ASXL1/SRSF2 co-mutated patients frequently harbored STAG2 mutations (42%), which were dependent on the presence of both ASXL1 and SRSF2 mutation (p < 0.05). STAG2 and SETBP1 mutations were also exclusive in ASXL1/SRSF2 co-mutated patients and associated with divergent chronic myeloid phenotypes. Our findings support that certain multi-mutant genotypes may be biologically relevant in ASXL1-mutated myeloid disease.