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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Fusion gene KMT2A::SEPTIN6 in AML cell line KOPM-88

ABSTRACT: KMT2A (alias MLL) is located at chromosomal position 11q23 and en-codes histone methyltransferase 2A which activates genes via methylation of histone H3 lysine K4 in their chromatin. Mutations of KMT2A, including partial tandem duplication (PTD) and fusion with partner genes are present in both lymphoid and myeloid acute leukemia. More than 100 different KMT2A fusion genes are described while only some of them are represented in cell line models. Cytogenetic and genomic copy number analyses, PCR, Western blot and RNA-sequencing were performed to characterize aberrations in acute myeloid leukemia (AML) cell line KOPM-88. Bioinformatic analysis of public AML patient data revealed differentially expressed genes. Functional analyses were performed in KOPM-88 by siRNA-mediated knockdown and life-cell imaging. AML cell line KOPM-88 is derived from a boy at relaps and has been reported to contain t(X;11)(q24;q23) with uncharacterized breakpoints. We identified in KOPM-88 fusion gene KMT2A::SEPTIN6 generated by this rearrangement and excluded KMT2A-PTD. KMT2A::SEPTIN6 activated BMP-signalling and inhibited expression of HOXA7 and HOXA9. BMP-signalling in turn activated cell proliferation by CDNK2B inhibition. KOPM-88 contains fusion gene KMT2A::SEPTIN6, representing the only cell line model for this type of KMT2A-rearrangement. KOPM-88 may serve to test novel therapeutic treatments for KMT2A::SEPTIN6-positive AML.

INSTRUMENT(S): Illumina NovaSeq X

ORGANISM(S): Homo sapiens

SUBMITTER: Claudia Pommerenke

PROVIDER: E-MTAB-17091 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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