Dataset Information

Loss of the NK Motif And AnKyrin Repeat Domain 1 (KANK1) leads to lymphoid compartment dysregulation in mice

ABSTRACT: The NK Motif And AnKyrin Repeat Domain 1 (KANK1) gene protein plays a role in the control of cytoskeleton formation by regulating actin polymerization. A t(5;9) translocation resulting in a fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) and KANK1 was detected in a patient with myeloid neoplasm (MN) characterized with severe thrombocythemia[2]. The protein is thought to have a tumour suppressor function, as its expression is downregulated or missing in several tumor tissues, while over-expressing the protein was reported to inhibit the proliferation of tumor cells in solid cancer models [3-5]. We established a novel germline loss of heterozygosity (LOH) mutation encompassing the KANK1 gene in a young Myelodysplastic syndrome (MDS) patient and his healthy father, with no additional MDS-related mutations or chromosomal abnormalities. Clinical investigation suggested development of MDS following severe infection, likely triggered by an autoimmune mechanism. The Kank1-/- mice remained healthy and did not develop any hematological abnormality. loss of Kank1 expression led to alteration in the cologenic and proliferative potential of murine BM cells and decrease in HSPCs population frequency. Comprehensive marker expression analysis of lineage cell populations indicated a role for Kank1 in lymphoid cells differentiation. Total protein analysis suggests the involvement of Kank1 in BM cells’ cytoskeleton formation and mobility.

INSTRUMENT(S): Orbitrap Eclipse, Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood

SUBMITTER: Erwin Schoof

LAB HEAD: Kirsten Groenbaek

PROVIDER: PXD045032 | Pride | 2024-01-26

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20210426_MK_SS_Marwa_689.raw	Raw
	20210426_MK_SS_Marwa_693.raw	Raw
	20210426_MK_SS_Marwa_695.raw	Raw
	20210426_MK_SS_Marwa_812_rerun.pdResult	Other
	20210426_MK_SS_Marwa_812_rerun.raw	Raw

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Publications

Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model.

Almosailleakh Marwa M Bentivegna Sofia S Narcisi Samuele S Benquet Sébasitien J SJ Gillberg Linn L Montaño-Almendras Carmen P CP Savickas Simonas S Schoof Erwin M EM Wegener Amelie A Luche Hérve H Jensen Henrik E HE Côme Christophe C Grønbæk Kirsten K

Genes 20231016 10

The KN Motif and AnKyrin Repeat Domain 1 (<i>KANK1</i>) is proposed as a tumour suppressor gene, as its expression is reduced or absent in several types of tumour tissue, and over-expressing the protein inhibited the proliferation of tumour cells in solid cancer models. We report a novel germline loss of heterozygosity mutation encompassing the <i>KANK1</i> gene in a young patient diagnosed with myelodysplastic neoplasm (MDS) with no additional disease-related genomic aberrations. To study the p ...[more]

PMID: 37895296

Similar Datasets

Project description:Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Noncoding-RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease. In this study, gene expression profiles of CD34+ and stromal cells of MDS patients with refractory anemia with ringed sideroblasts (RARS) subgroup were compared those of healthy individuals, using 44k combined intron-exon oligoarrays, which included probes for protein-coding genes, for sense and antisense strands of totally intronic noncoding (TIN) and for partially intronic noncoding (PIN) RNAs. In CD34+ cells of MDS-RARS patients, 217 genes were significantly differentially expressed (q-value < 0.01) in comparison to healthy individuals, of which 68 (31%) were noncoding transcripts. In stromal cells of MDS-RARS, 13 genes were significantly differentially expressed (q-value < 0.05) in comparison to healthy individuals, of which 4 (30%) were noncoding transcripts. These results demonstrated, for the first time, in CD34+ cells and stromal cells the differential ncRNA expression profile between MDS-RARS and healthy individuals, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes. Bone marrow (BM) CD34+ cell samples were collected from 4 healthy subjects and from 4 MDS patients. Stromal samples were collected from 4 healthy subjects and 3 MDS patients. All patients were diagnosed as RARS according to the French-American-British (FAB) classification and did not present chromosomal abnormalities; they received no growth factors or any further MDS treatment.