Welcome to the MDS 2021 Interactive Programme
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Introduction (ID 232)
CHIP, CCUC/ICUS as models of clonal progression (ID 27)
Genetic basis for leukemia development (ID 28)
Oral Presentation: Combined Landscape of Single-Nucleotide Variants and Copy-Number Alterations in Clonal Hematopoiesis: Analysis in 11,234 Japanese Individuals (ID 152)
Abstract
Background And Aims
Clonal hematopoiesis (CH) in apparently healthy individuals has recently been highlighted and implicated in the development of hematological malignancies (HM) and cardiovascular mortality. In previous studies, CH has been investigated through detecting either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both.
Methods
Here, we performed a combined analysis of CH-related SNVs/indels and CNAs in 11,234 individuals aged ≥60 years (a median of 70), including 672 with subsequent HM events, to delineate their relationships and impacts on clinical outcomes.
Results
Detected in 40% of the subjects, CH-related SNVs/indels and/or CNAs were significantly cooccurred in the same individuals. CH-related SNVs/indels and CNAs coordinately affected blood cell counts and the mortality from HM, depending on the maximum clone size and total number of both lesions (Figure1). In particular, as is the case with those in myeloid neoplasms, SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2, and TP53 significantly co-occurred and led to bi-allelic alterations in these genes in the early leukemogenesis, predicting a high HM mortality. CH-related SNV/indels were also associated with the risks of hypertension and cardiovascular mortality. This association was more prominent when SNVs/indels were combined with CNAs, even though cardiovascular mortality was not affected by CNAs alone (Figure2).
Conclusions
These findings provided novel insight into the interplay between SNVs/indels and CNAs in CH, highlighting the importance of detecting both types of lesions in the evaluation of CH.