Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background

Abstract

Primary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.

Transcriptomic Analysis in Multiple Myeloma and Primary Plasma Cell Leukemia with t(11;14) Reveals Different Expression Patterns with Biological Implications in Venetoclax Sensitivity

“…Several studies investigating the gene mutation patterns [ 6 ] and differential gene and miRNAs expression profiles [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ], compared to pPCL and MM at molecular and biological levels. Overall, pPCLs have elevated genomic instability, especially for karyotypic complexity, and a higher prevalence of 17p13 deletions and 1q gains compared to MMs.…”

The Significance of mRNA in the Biology of Multiple Myeloma and Its Clinical Implications

“…Studies based on GEP have been widely used to better understand the biology of MM by identifying the genes involved in the molecular pathogenesis of the disease and their clinical significance, to predict survival in multiple myeloma and to identify patients who will benefit from particular types of therapy. Some groups even made an attempt to compare the transcriptome of MM and primary plasma cell leukemia: a more aggressive form of plasma cell dyscrasia [33]. Expression profiles of differentially expressed genes are of critical importance and have provided insights into MM biology.…”

The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia

“…The results of transcriptome analysis reveal a significant deviation between the two types of tumors. Interestingly, most of the differences were observed in the spliceosome machinery genes, which emphasizes the cell type- specificity of alternative splicing [ 39 ].…”