According to an abstract recently posted in the journal Blood, a team of scientists has discovered novel genes that affect the development of aberrant mast cells in patients with systemic mastocytosis (SM).

The study presented at the 64th ASH Annual Meeting aimed to investigate the pathogenic mechanism behind SM from the process of hematopoietic development and the origin of abnormal mast cells.

The researchers performed a multiomics study of bone marrow progenitors from SM, combining oligo-conjugated surface antibodies with single-cell transcriptomic data. By fluorescence-activated cell sorting, enriched KIThigh mast cells hashing with oligo-barcoded antibodies together with a spectrum of lineage KIT+ hematopoietic progenitors were isolated from bone marrow samples.

Read more about SM etiology

For the purpose of this study, the researchers stained all cells using oligo-conjugated surface antibodies including CD25 and CD2 aberrant mast cell characteristic markers prior to sequence, the authors noted.

The combined analysis of both oligo-tagged antibody and transcriptome data of CD25 (IL2RA) successfully pinpointed the aberrant mast cells and the phenotypically normal ones.

“Comparative analysis between these 2 populations revealed a series of novel markers that could provide insights in understanding pathogenic mechanisms and offer possible new therapeutic targets,” the study authors wrote.

The investigators set out to explore the role of stem cell factor receptor (KIT) D816V mutations in aberrant mast cell formation. In doing so, they used long-read sequencing. By integrating long-read sequencing and transcriptome data, this analysis provided insight into the mutational profile of each cell in the hematopoietic landscape.

The main genetic contributor to SM is the D816V mutation, leading to constitutive tyrosine kinase activation, abnormal proliferation and activation of mast cells, and a series of clinical symptoms.


Wu C, Boey D, Mo J, et al. Single-cell multi-omics analysis reveals hematopoiesis of aberrant mast cells in systemic mastocytosis. Blood. Published online November 15, 2022. doi:10.1182/blood-2022-170025