Clonal hematopoiesis: Molecular and clinical implications

A Synopsis Clonal Hematopoiesis of Indeterminate Potential in Hematology

“…Whole exome sequencing (WES) or targeted gene panels are both used to search for somatic mutations in hematopoietic cells. Whole genome sequencing and WES are generally less sensitive as compared with targeted exome sequencing which looks for specific mutations in the coding region of genes known to be implicated in CHIP [ 10 ]. For example, it was noted that WES can detect clonal hematopoiesis (CH) in 10–15% of individuals older than 70 years (with variant allele frequency (VAF) of 3–10%) as compared with 25–75% prevalence when using targeted NGS [ 5 , 11 , 12 ].…”

“…Although their frequencies vary among studies, the three most common implicated genes are DNMT3A , TET2 , and ASXL1 (collectively known as “DTA mutations”) [ 6 ]. All three of these genes are epigenetic modulators, but two of them have opposing functions: while the DNMT3A enzyme catalyzes cytosine methylation, TET2 catalyzes cytosine demethylation [ 10 ]. Other commonly mutated genes include TP53 , JAK2 , SF3B1 , GNAS , PPM1D , and BCORL1 [ 4 ].…”

“…Other commonly mutated genes include TP53 , JAK2 , SF3B1 , GNAS , PPM1D , and BCORL1 [ 4 ]. These genes have a broad array of cellular functions including signal transduction, premRNA splicing, and DNA repair (see Table 1 ) [ 10 , 17 ].…”

“…The PPM1D gene mutation is mostly found in cell clones that have been exposed to chemotherapeutic agents [ 14 ]. ASXL1 mutations are mostly associated with smoking [ 10 ].…”

“…ASXL1 mutations are mainly reported in smoking patients [ 10 ]. ASXL1 is a gene that is frequently mutated during CH or hematological malignancies, even though it has no clear catalytic activity.…”