Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq of Breast Implant-Associated Anaplastic Large Cell Lymphoma

ABSTRACT: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an anaplastic lymphoma kinase-negative (ALKneg) T-cell lymphoma. Here, we provide RNA-seq data of four BIA-ALCL and four ALCL cell lines:TLBR-1, TLBR-2, TLBR-3, TLBR-4 and DEL (two replicates), KARPAS-299, KI-JK, SUP-M2 (two replicates), respectively.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Claudia Pommerenke

PROVIDER: E-MTAB-14735 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PI3K/AKT inhibitor BEZ-235 targets CCND2 and induces G1 arrest in breast implant-associated anaplastic large cell lymphoma.

Nagel Stefan S Fischer Anja A Bens Susanne S Hauer Vivien V Pommerenke Claudia C Uphoff Cord C CC Zaborski Margarete M Siebert Reiner R Quentmeier Hilmar H

Leukemia research 20230827

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a mature, CD30-positive T-cell lymphoma lacking expression of the anaplastic lymphoma kinase (ALK). In contrast to ALK-positive ALCL, BIA-ALCL cells express cyclin D2 (CCND2) which controls cyclin dependent kinases 4 and 6 (CDK4/6). DNA methylation and expression analyses performed with cell lines and primary cells suggest that the expression of CCND2 in BIA-ALCL cell lines conforms to the physiological status of differentiat ...[more]

PMID: 37647808

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Project description:Homeobox genes encode transcription factors regulating basic processes in cell differentiation during embryogenesis and in the adult. Recently, we have reported the NKL-code which describes physiological expression patterns of nine NKL homeobox genes in early hematopoiesis and in lymphopoiesis including main stages of T-, B- and NK-cell development. Aberrant activity of NKL homeobox genes is involved in the generation of hematological malignancies including T-cell leukemia. Here, we searched for deregulated NKL homeobox genes in main entities of T-cell lymphomas comprising peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL), hepatospleenic T-cell lymphoma (HSTL), and NK/T-cell lymphoma (NKTL). Our data revealed in all types altogether 19 aberrantly overexpressed genes, demonstrating that deregulated NKL homeobox genes play a significant role in T-cell lymphomas as well. For detailed analyses we focused on NKL homeobox gene MSX1 which is normally expressed in NK-cells and aberrantly activated in T-cell leukemia. This gene was overexpressed in subsets of HSTL patients and HSTL-derived sister cell lines DERL-2 and DERL-7 which served as models to identify mechanisms of deregulation. We performed genomic and expression profiling and whole genome sequencing and revealed mutated and deregulated gene candidates including the fusion gene CD53-PDGFRB exclusively expressed in DERL-2. Subsequent knockdown experiments allowed the construction of an aberrant network involved in MSX1 deregulation containing chromatin factors AUTS2 and H3B/H3.1, PDGF- and BMP-signalling pathways, and homeobox genes NKX2-2 and PITX1. The gene encoding AUTS2 is located at 7q11 and may represent a basic target of the HSTL hallmark aberration i(7q). Our data indicate both oncogenic and tumor suppressor functions of MSX1 in HSTL, reflecting its activity in early lineage differentiation of T- and NK-cells and the presence of NK-cell like characteristics in malignant HSTL cells. In this context, NKL homeobox gene MSX1 may represent a selective target in HSTL tumor evolution. Together, the data highlight an oncogenic role of deregulated NKL homeobox genes in T-cell lymphoma and identified MSX1 as a novel player in HSTL, involved in aberrant NK- and T-cell differentiation.

Dataset Information

RNA-seq of Breast Implant-Associated Anaplastic Large Cell Lymphoma

Publications

PI3K/AKT inhibitor BEZ-235 targets CCND2 and induces G1 arrest in breast implant-associated anaplastic large cell lymphoma.

Similar Datasets

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