Concurrence of Myelodysplastic syndromes and large granular lymphocyte leukemia: clinicopathological features, mutational profile and gene ontology analysis in a single center

The concurrence of Myelodysplastic syndromes (MDS) and large granular lymphocyte leukemia (LGLL) has been reported in a small group of patients and might suggest an etiologic relationship rather than a simple coincidence. In this present study, clinicopathological features were detailed in ten cases of MDS concurrent with LGLL (MDS-LGLL). These cases included seven patients with T-LGLL, two with mixed-phenotype LGLL, and one with CLPD-NK. Subsequently, gene mutation screening for commonly myeloid-related or lymphoid-related genes was performed in MDS-LGLL patients by using next generation sequencing (NGS). The genes with the highest frequency of mutations were (3/10, 30%) and (3/10, 30%) among a panel of 114 genes. LGLL-associated mutations of (2/10, 20%) and (1/10, 10%) were also detected. Moreover, whole-exome sequencing (WES) and gene ontology (GO) analysis for one patient in his different phases revealed increased enrichment of histone H3 lysine 4 (H3K4) mono-methylation (GO:0097692) pathway and decreased enrichment of translocation of ZAP-70 to immunological synapse (R-HAS-202430) pathway upon progression from MDS to MDS-LGLL.