Framework of clonal mutations concurrent with WT1 mutations in adults with acute myeloid leukemia (Alliance)|白血病数据集|基因突变数据集

Mutations affecting the tumor suppressor gene, WT1 transcription factor (WT1) are relatively common in adults with acute myeloid leukemia (AML) and have been reported to associate with a poor prognosis.  However, there is limited data describing additional mutations co-occurring with WT1 as well as clonal architecture and complexity.  We performed targeted DNA sequencing on 96 pretreatment samples from adult patients with de novo AML who harbored WT1 mutations and subsequently performed single-cell DNA sequencing on a subset of these samples. FLT3-ITD mutations were the most common co-occurring mutations detected in 47% of WT1-mutated patients (WT1mut/FLT3-ITD).  Among WT1mut/FLT3-ITD patients, NPM1 mutations were observed in 58% of patients. In contrast, patients with WT1-mutated AML but no FLT3-ITD (WT1mut/no FLT3-ITD) had significantly more frequent mutations in alternative signal activating pathways (FLT3-TKD: 25% vs 11%; and NRAS: 37% vs 11%) compared with WT1mut/FLT3-ITD patients,..., For single-cell DNA sequencing, the MissionBio (San Francisco, CA) acute myeloid panel was utilized. Total cells were diluted to a concentration 3,500 cells/μL in Cell Buffer and the Tapestri® single-cell DNA sequencing user guide was followed. The final normalized libraries were sequenced using 2x300bp paired-end multiplexed runs on the Illumina MiSeq platform. Tapestri® Analysis pipeline was utilized to process and analyze the sequencing fastq files to generate .loom files. LOOM files were then visualized in Tapestri® Insight to call variants and visualize clones., Tapestri Insights
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