Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

“…The early secretory cluster expressed both epithelial (EPCAM, KRT19) and mesenchymal (THY1, DCN) characteristics as well as smooth muscle actin and estrogen receptor, and thus bore some similarities to myoepithelial cells of the uterus. This population expresses IGFBP5 and LGALS1, genes implicated in homeostasis of stem and/or progenitor populations in normal and diseased tissues (Byrd et al, 2019;Garcés et al, 2020;Tumbar et al, 2004;You et al, 2018) and MEG3, an imprinted long noncoding RNA. Previous reports have identified an enrichment of stem cells in the fimbrial portion of the tube (Paik et al, 2012).…”

Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications

“…Nonetheless, in one study, the frequency of CTPC in blood increased to 96% of newly-diagnosed MM patients when RNA was used instead of DNA to detect tumor IGH -V(D)J gene rearrangements [ 114 ]. However, to date, molecular analysis by next generation sequencing of blood-derived CTPC has preferentially focused on the molecular characterization of purified CTPC in order to better understand the biology of the disease [ 119 , 121 , 137 , 138 , 139 ]. In this regard, a recent study based on single-cell RNA sequencing reported that overexpression of CENPF and LGALS1 genes in CTPC from MM patients was associated with reduced progression free survival rates [ 119 ] ( Table 3 ).…”

“…However, to date, molecular analysis by next generation sequencing of blood-derived CTPC has preferentially focused on the molecular characterization of purified CTPC in order to better understand the biology of the disease [ 119 , 121 , 137 , 138 , 139 ]. In this regard, a recent study based on single-cell RNA sequencing reported that overexpression of CENPF and LGALS1 genes in CTPC from MM patients was associated with reduced progression free survival rates [ 119 ] ( Table 3 ). In contrast, the clinical impact of next generation sequencing-based analysis of CTPC in MGUS, SMM and other plasma cell neoplasms currently remains unknown and deserves further investigation [ 137 ].…”

“…For decades, the association observed between the presence (and greater numbers) of CTPC in blood and a higher tumor burden in the BM of MGUS, MM, PCL and other plasma cell neoplasms, has led to the notion that CTPC are a functionally unique population of BM-derived tumor PC [ 20 , 23 , 24 ]. However, more recent data indicates that CTPC usually represent a distinct subclone of BM PC [ 119 , 143 , 144 ] with a more immature phenotype ( Figure 3 ) and quiescent profile [ 21 , 144 , 145 ]. Thus, the association between blood and BM PC numbers could not be confirmed in several studies [ 20 , 118 , 129 ], or it has been shown to be a non-linear correlation [ 21 , 32 ] independent of sample quality (e.g., hemodilution).…”

“…From a genomic point of view, several studies have shown that (purified) CTPC (mostly) from MM patients reproduce the pattern of somatic mutations present in BM tumor PC with relatively high levels of (sub)clonal heterogeneity [ 137 , 143 ]. Thus, CTPC show overexpression of genes (and mutations/genetic alterations) associated with drug resistance [ 143 ], the inflammatory response (e.g., BIRC3 or TNFAIP 3), hypoxia (e.g., DDIT4 ), cell migration (e.g., CFAP54 , EZR , EMP3 or AHNAK ) and metastasis (e.g., AGR2 , DDX5 , MALAT1 , TMED2 , TPT1 ), together with downregulation of genes responsible for progression through the cell cycle (e.g., CENPF or CDC6 ) [ 119 ] ( Figure 4 A). In addition, the presence of CTPC in blood has also been related to ancestral cytogenetic profiles and unique cytogenetic alterations, including t(4;14) [ 28 , 29 , 116 ], deletion 13q [ 29 ], deletion 17p, t(11;14) and t(14;16) [ 22 ] ( Figure 4 B).…”