Abstract 772P
Background
Clonal hematopoiesis of undetermined significance (CCUS) is defined as persistent cytopenia that is not explained by other causes accompanied by clonal hematopoiesis (CH). We aimed to investigate the differences in mutation profiles associated with clinical features between CCUS and myelodysplastic syndrome (MDS) in patients with cytopenia.
Methods
We included patients with persistent one or more cytopenia who underwent next-generation sequencing (NGS) at our institution. Hybrid capture-based NGS was performed using custom probes targeting 30- or 531- hematologic cancer-related genes (Dxome, Seongnam, Korea) and NextSeq 550Dx Instrument (Illumina, CA, USA). Somatic variants were categorized as tiers 1, 2, or 3 based on oncogenicity and clinical significance according to AMP/ASCO/CAP guidelines.
Results
A total of 371 patients were included in this study. 199 MDS and 44 CCUS patients were included. More than two thirds of patients with MDS had at least one tier 1/2 somatic variant (142 out of 199 patients; 71.4%). The average number of mutations was 1.7 in MDS and 1.4 in CCUS. The number of patients for ASXL1, DNMT3A, EZH2, RUNX1, and SF3B1 were significantly different in MDS and CCUS (p < 0.05). Among these genes, ASXL1, EZH2, RUNX1 and SF3B1 showed a higher number of mutated patients (%) in MDS, while DNMT3A mutated patients (%) were higher in CCUS. For TP53 and TET2, variant allele frequency (VAF%) was different in MDS and CCUS groups. The median VAF was 28.8% in MDS and 0.4% in CCUS for TP53, and 18.5% in MDS and 2.6% in CCUS for TET2.
Conclusions
We found similarities and differences in the genetic architecture of MDS and CCUS. Understanding the genetic abnormalities of CCUS could help us understand the pathophysiology of CH and the mechanisms of progression to hematologic malignancies such as MDS. Additional research about the specific genetic features of CCUS is needed to diagnose and manage cytopenia patients appropriately.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Lee, J.R. Choi: Financial Interests, Personal, Full or part-time Employment: Dxome. All other authors have declared no conflicts of interest.