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Progenitor-like cell type of an MLL-EDC4 fusion in acute myeloid leukemia.

ABSTRACT:

SUBMITTER: Schuster LC

PROVIDER: S-EPMC10694518 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Progenitor-like cell type of an MLL-EDC4 fusion in acute myeloid leukemia.

Schuster Linda C LC Syed Afzal P AP Tirier Stephan M SM Steiger Simon S Seufert Isabelle I Becker Heiko H Duque-Afonso Jesus J Ma Tobias T Ogawa Seishi S Mallm Jan-Philipp JP Lübbert Michael M Rippe Karsten K

Blood advances 20231101 22

PMID: 37820244

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Progenitor like cell type of an MLL-EDC4 fusion in acute myeloid leukemia

Project description:Transcriptome analysis by single cell sequencing provides valuable information on intratumor heterogeneity and developmental stages of acute myeloid leukemia (AML) as well as interactions of tumor cells with the microenvironment. However, it has been hardly applied to the subgroup of cases with translocations of the mixed lineage leukemia (MLL) gene for which the enhancer of mRNA decapping 4 (EDC4) gene was recently identified as a novel fusion partner (MLL-EDC4). Here, we compared different MLL translocation by single cell RNA sequencing of cells derived from peripheral blood. The AML MLL-EDC4 patient almost exclusively showed a transcriptional profile of hematopoietic progenitor cells while leukemic cells while the MLLT3-MLL and MLL-ELL fusions exhibited a more differentiated phenotype. The MLL-EDC4 progenitor state was characterized by the upregulation of key transcriptional regulators in AML (RUNX1, SOX4, HOPX), target genes of MYC and interferon signaling as well as other genes known to play a critical role in hematopoiesis or leukemic stem cell activation (CDK6, FLT3, NPM1). In addition, we detected an enrichment of a normal and putatively immunosuppressive monocyte population in the patient with MLL-EDC4. Thus, the MLL-EDC4 translocation was associated with unique transcriptional and microenvironmental features.

2022-09-29 | GSE214240 | GEO