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Letters to the Editor
Supplementary Figure S2 illustrates the workflow. Median age was 69 years (range, 17-94 years) and two-thirds were male. Sixty-four patients (42%) had ≥1 mutation(s) in MDS-related genes with the most commonly affected genes being TET2, DNMT3A and SRSF2 (Online Supplementary Table S2).
SNP-A identified a total of 25 structural aberrations (excluding loss of the Y chromosome [LOY]); 12 dele- tions, eight CNLOH and five gains, in 23 of 153 patients (15%) (Online Supplementary Table S3, Online Supplementary Figure S3).
Median sizes of the aberrations were deletions: 248 Kb (range, 131.6-2,867.5 Kb), CNLOH: 82.9 Mb (range, 11.6- 137.1 Mb) and gains: 1.3 Mb (range, 0.6-2.6 Mb) ranging from minor genomic segments to entire chromosomes.
Mutations in MDS-related genes were present in 12 of
23 patients (52%) with CNA/CNLOH (Online Supplementary Table S3). Thus, a marker of clonal hematopoiesis was identified in 11 of 85 ICUS patients (13%) in whom no abnormalities were detected by con- ventional cytogenetics or targeted sequencing (Online Supplementary Figure S4).
The CNA/CNLOH identified in the ICUS patients were largely overlapping with recurrent CNA/CNLOH of known or likely clinical significance in patients with myeloid malignancies (10 of 25 CNA/CNLOH; 40%) (Table 1A).3,4,6 Correspondingly, many genes frequently mutated in MDS, myeloproliferative neoplasms and/or AML were located within the sites of CNA/CNLOH (Table 1B; Online Supplementary Figure S5).
Mean corpuscular volume (median, 97 vs. 90 fL; P=0.014) and ferritin level (median, 260 vs. 173 mg/L;
A
B
Figure 2. In patienst with clonal cytopenia of undetermined significance, the presence of additional structural aberrations is associated with an increased haz- ard of all-cause mortality in univariable and multivariable analysis. (A) Kaplan-Meier estimates of overall survival of the group of clonal cytopenia of undeter- mined significance (CCUS) patients with copy number aberrations (CNA) or copy neutral loss of heterozygosity (CNLOH) (excluding loss of the Y chromosome; red curve) and the group of CCUS patients without CNA or CNLOH (black curve). (B) Forest plot of hazard ratios (HR) including 95% Confidence Intervals (CI) for all-cause mortality in multivariable analysis in CCUS patients (n=51 with complete data). Overall survival was measured from first bone marrow investigation (=inclusion) to death from any cause. Patients alive at the last date of follow-up were censored at that time. Annotated P-values are from two-sided log-rank tests. Severe anemia was defined as hemoglobin <100 g/L.
haematologica | 2021; 106(6)