Cytogenetic and Genetic Abnormalities with Diagnostic Value in Myelodysplastic Syndromes (MDS): Focus on the Pre-Messenger RNA Splicing Process

• Published in: Diagnostics (Basel) Vol. 12; no. 7; p. 1658
• Main Authors: Douet-Guilbert, Nathalie, Soubise, Benoît, Bernard, Delphine G, Troadec, Marie-Bérengère
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.07.2022; MDPI
• Subjects: Bone marrow; Cell cycle; chromosome abnormalities; Chromosomes; Classification; Cytogenetics; del(5q); Diagnosis; Gene mutations; Genes; Genetic aspects; Health aspects; Life Sciences; Medical research; Medicine, Experimental; Messenger RNA; Mutation; myelodysplasia; Myelodysplastic syndromes; Pathogenesis; Proteins; Review; RNA splicing; SF3B1; splicing; France; myelodysplasia; diagnosis; U2AF1; splicing; PRPF8; SF3B1; SLU7; chromosome abnormalities; del(5q); LUC7L2; RBM22
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics12071658

Myelodysplastic syndromes (MDS) are considered to be diseases associated with splicing defects. A large number of genes involved in the pre-messenger RNA splicing process are mutated in MDS. Deletion of 5q and 7q are of diagnostic value, and those chromosome regions bear the numbers of splicing genes potentially deleted in del(5q) and del(7q)/-7 MDS. In this review, we present the splicing genes already known or suspected to be implicated in MDS pathogenesis. First, we focus on the splicing genes located on chromosome 5 ( , , , , ), chromosome 7 ( ), and on the gene since both chromosome aberrations and the mutation are the only genetic abnormalities in splicing genes with clear diagnostic values. Then, we present and discuss other splicing genes that are showing a prognostic interest ( , , , , and ). Finally, we discuss the haploinsufficiency of splicing genes, especially from chromosomes 5 and 7, the important amplifier process of splicing defects, and the cumulative and synergistic effect of splicing genes defects in the MDS pathogenesis. At the time, when many authors suggest including the sequencing of some splicing genes to improve the diagnosis and the prognosis of MDS, a better understanding of these cooperative defects is needed.