Fig. 1: Myeloid clones with 5q and 7q deletions have complex genomes, biallelic pathogenic/likely pathogenic TP53 variants and poor overall survival.

A Schematic of cohort. One hundred and three cases from patients with a diagnosis of a myeloid malignancy and with conventional chromosome and/or FISH studies demonstrating either normal karyotype (NK), 7q deletion (7q del), 5q deletion (5q del), 5q and 7q deletion (5q/7q del). Eighty-nine patients had sequencing (NGS or PCR-based) to identify sequence variants, 69 had MPseq to identify CNV and SV, and 95 samples had data available for assessment of overall survival. B Circos plots depicting CNVs and SVs detected by MPseq in each subtype. The outermost histogram (red) displays genomic losses, with axes rings representing the 20, 40, 60, 80, and 100% number of events per 1Mb window. The next histogram (blue) displays genomic gains, with axes rings representing the 20, 40, 60, 80, and 100% number of events per 1Mb window. Inner links (black) represent translocation and inversion events, with lines indicating positions along the chromosome. C TP53 deletion determined by FISH or MPseq and single nucleotide variant (SNV) status. Biallelic status requires evidence of deletion and SNV, or two pathogenic/likely pathogenic SNVs or one SNV over 80% VAF. D Overall survival probability using NK, 5q and 7q patient status (N = 95 samples) and in E. TP53 variant status (N = 81). Survival curves analysis was done using the Kaplan–Meier method and Log rank (Mantel–Cox) was run to determine the difference in the survival distribution among all four study subtypes. Eight patients were removed due to lack of follow-up data. Survival and AML diagnosis date was obtained from the medical record. The date of diagnosis reflects the original AML diagnosis. In D, 5q/7q del (blue line), 5q del (green line), 7q del (red line), and NK (purple line). In E, biallelic TP53 variants (blue line), monoallelic TP53 variants (green line), and normal TP53 status (red line).