Next‐generation sequencing in hypoplastic bone marrow failure: What difference does it make?

Abstract

Hypoplastic bone marrow failure is a diagnostic feature of multiple haematological disorders, which also share a substantial overlap of clinical symptoms. Hence, discrimination of underlying disorders in patients presenting with hypoplastic bone marrow failure remains a major challenge in the clinic. Recent next‐generation sequencing (NGS) studies have broadened our understanding of the varying molecular mechanisms and advanced diagnostics of disorders exhibiting hypoplastic bone marrow failure. In this article, we present a literature review of NGS studies of haematological disorders associated with hypoplastic bone marrow failure and highlight the relevance of NGS for improved clinical diagnostics and decision‐making.

Myelodysplastic syndromes and overlap syndromes

“…In the study, SF3B1, TET2, DNMT3A, and SRSF2 mutations were the most prevalent in h-MDS [118,121]. In addition, a significantly higher prevalence of PNH clones was present among the patients with h-MDS compared with non-hMDS [118,121]. It is reported that 20% to 35% of AA patients have somatic mutations associated with hematologic malignancies, most characteristically in the ASXL1, BCOR, and BCORL1 genes [122].…”

“…The largest study illustrated that 38% of patients with h-MDS harbored at least one somatic mutation, albeit with a lower number of mutations per patient when comparing h-MDS with non-hMDS [118,121]. In the study, SF3B1, TET2, DNMT3A, and SRSF2 mutations were the most prevalent in h-MDS [118,121]. In addition, a significantly higher prevalence of PNH clones was present among the patients with h-MDS compared with non-hMDS [118,121].…”

“…The genomic landscape of hMDS resulted in-between AA and non-hMDS in terms of the number of somatic mutations (AA＜hMDS＜non-hMDS), variant allele frequency (AA＜ hMDS＜non-hMDS), and involved genes (Table 10) [117]. The largest study illustrated that 38% of patients with h-MDS harbored at least one somatic mutation, albeit with a lower number of mutations per patient when comparing h-MDS with non-hMDS [118,121]. In the study, SF3B1, TET2, DNMT3A, and SRSF2 mutations were the most prevalent in h-MDS [118,121].…”

An atypical patient with bone marrow failure syndrome‐2 without microcephaly and learning disability in a Chinese family

“…12 Next-generation sequencing technology has accelerated the accurate molecular genetic testing of IBMFS. 13 The discovery of disease-associated gene mutations could also optimize fertility patterns and prevent pathogenic genes from influencing the physical health of the next generation. IBMFS patients carrying germline mutations have an increased risk of transformation to myelodysplastic syndrome and acute myeloid leukaemia, 14 while the early administration of allo-HSCT in patients with ERCC6L2-associated IBMFS might obtain better outcomes.…”

ERCC6L2-related disease: a novel entity of bone marrow failure disorder with high risk of clonal evolution

“…Some of these disorders present a variable risk of clonal evolution and progression to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) [9]. The biological study of these variants is leading to a deeper understanding of the genetic origin and pathogenesis of these diseases, eliciting new diagnostic categorization of BMF [10,11]. The different genetic driving mutations underpinning these entities result in highly different hematological phenotype with a different temporal evolution which is often difficult to predict.…”