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). In our study published in Blood Advances (Schuster et al., 2023; https://doi.org/10.1182/bloodadvances.2022009096), we compared different MLL translocations by single cell RNA sequencing of cells derived from peripheral blood or bone marrow. The MLL-EDC4 positive cells almost exclusively showed a transcriptional profile of hematopoietic progenitor cells while leukemic cells of MLL-MLLT3 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). Here, the scRNA-seq dataset of our study is provided. It contains six scRNA-seq read count matrices of the AML samples with MLL fusions as described in the table scRNA-seq_samples.xlsx. Further details are given in the publication associated with this dataset.