KCTD15 is overexpressed in human childhood B-cell acute lymphoid leukemia

Abstract

Leukemic cells originate from the malignant transformation of undifferentiated myeloid/lymphoid hematopoietic progenitors normally residing in bone marrow. As the precise molecular mechanisms underlying this heterogeneous disease are yet to be disclosed, the identification and the validation of novel actors in leukemia is of extreme importance. Here, we show that KCTD15, a member of the emerging class of KCTD ((K)potassium Channel Tetramerization Domain containing) proteins, is strongly upregulated in patients affected by B-cell type acute lymphoblastic leukemia (B-ALL) and in continuous cell lines (RS4;11, REH, TOM-1, SEM) derived from this form of childhood leukemia. Interestingly, KCTD15 downregulation induces apoptosis and cell death suggesting that it has a role in cellular homeostasis and proliferation. In addition, stimulation of normal lymphocytes with the pokeweed mitogen leads to increased KCTD15 levels in a fashion comparable to those observed in proliferating leukemic cells. In this way, the role of KCTD15 is likely not confined to the B-ALL pathological state and extends to activation and proliferation of normal lymphocytes. Collectively, data here presented indicate that KCTD15 is an important and hitherto unidentified player in childhood lymphoid leukemia, and its study could open a new scenario for the identification of altered and still unknown molecular pathways in leukemia.

lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

“…The intersection of the PCA–based 584 lncRNAs with the 873 differentially expressed genes (DEGs) from the transcriptome dataset [ 33 ] resulted in 30 differentially expressed lncRNAs (DElncRNAs, Table 1 ), hereinafter referred only as candidate lncRNAs…”

“…As mentioned above, the PCA, combined with differential expression analysis, prioritized 30 lncRNAs able to distinguish B–ALL patients from healthy subjects. To predict lncRNAs function, we firstly carried out functional enrichment analyses using the protein–coding genes (PCGs) differentially expressed in B–ALL relative to normal samples from RNA–Seq data [ 33 ] hereinafter referred as PCGs. Figure 4 A results showed the top 20 clusters of the most statistically significant enriched terms from multiple ontologies, i.e., gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome database ranked for statistical significance.…”

“…However, few B–ALL–related lncRNAs have been characterized by their functional roles [ 15 , 52 ] and the lncRNA’s involvement in B–ALL development and/or progression as well as how they may orchestrate the B–ALL transcriptome landscape along with the protein–coding genes (PCGs) is far to be fully elucidated. In this context, we attempted to fill this knowledge gap by exploiting the transcriptome dataset already published by our research group [ 33 ] (Bioproject: PRJNA601326) for evaluating possible functional cooperation of lncRNAs with mRNAs. Our in–silico and ex vivo study aims to prioritize lncRNA signature as diagnostic biomarkers for paediatric B–ALL.…”

“…Expression profiles of healthy circulating naive B cells and leukemic cells of children affected by common B–cells of children acute lymphoid leukaemia (B–ALL) are described in [ 33 ]. RNA–Seq fastq files are available at Bioproject PRJNA601326.…”

“…Recently, our group highlighted KCTD15, a Potassium Channel Tetramerization Domain Containing 15 protein, over–expressed in childhood B–ALL patients compared with healthy subject samples through RNA–Sequencing experiments (RNA–Seq) (Bioproject: PRJNA601326) [ 33 ].…”