Single cell transcriptomics reveals tumor heterogeneity in myeloid
leukemia associated with Down syndrome
Abstract
Background: The susceptibility of children with Down syndrome
to acute myeloid leukemia especially acute megakaryocytic leukemia
(AMKL) is much higher than that of general population. The origination
of ML-DS (Myeloid leukemia associated with Down syndrome) cells, the
occurrence, development and tumor heterogeneity of ML-DS are still
[ambiguous](javascript:;). For children with DS, the incidence of
non-AMKL ML-DS is relatively rare, and there is little research on the
pathogenesis of this type of leukemia. Methods: Our study for
the first time using single-cell RNA sequencing (Sc-RNA seq) technology
to analyze the transcriptome of peripheral blood tumor cells from
patients with non-AMKL type ML-DS. Transcriptome analysis of 2202
peripheral blood cells from one patient with non-AMKL ML-DS were
conducted, and the genetic characteristics of leukemia cells were
examined in detail. Results: We reveal that LMO4, CPA3, RAD21,
POU2F2, KIT, and ANXA1 were highly expressed in cluster 0, which
exhibited heightened stem cell characteristics. During the
differentiation of various tumor cell clusters, the expression levels of
CPA3, FCER1A, HPGD, HPGDS, LAPTM5, and LMO4 exhibited significant
difference during the differentiation of different tumor cell clusters.
KEGG pathway enrichment analysis shows that aml-0 subsets are
significantly enriched in microRNAs in cancer pathway, which play a key
role as post transcriptional regulators in leukemogenesis.
Conclusion: Above all, the differential gene expression
characteristics of different tumor cell subpopulations of interest were
analyzed at the single cell level to the heterogeneity of tumor cells
and the different characteristics of subpopulations, and to discover
potential cell stem gene markers.