Abstract
Mixed-phenotype acute leukemia (MPAL) is a progenitor type of leukemia with ambiguous expression of lineage markers. The diagnosis of MPAL is based on flow cytometric analysis of immunophenotype, which commonly identifies myeloid lineage markers as well as B- or T- lymphoid lineage markers on leukemic blasts. Due to the rare occurrence of this disease, few studies have delineated the molecular bases of MPAL. Combining conventional karyotyping with whole genomic sequencing (WGS) and RNA sequencing (RNA-seq), we report here our identification and characterization of chromosome translocations, gene mutations and gene expression profile in four patients with T/Myeloid MPAL, including two t(6;14)(q25;q32) one t(8;14)(q24.2;q32) and one t(7;8)(p14;q24.2). Notably, seven of the eight translocation breakpoints reside in the non-coding regions and their locations appear to be shared by two or more patients. Gene expression analysis of matched diagnostic vs. remission samples provided evidence of transcriptomes alteration involving nucleosome organization and chromatin assembly.