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Frequent derepression of the mesenchymal transcription factor gene in acute myeloid leukemia (human)

ABSTRACT: Bone marrow samples from normal adult male donors were collected into EDTA. Red cells were removed by ammonium chloride lysis. Leukocytes were washed in SM buffer and CD34+ cells were separated from CD34- cells using an AutoMACS device and anti-CD34 immunomagnetic beads (Miltenyi Biotec), according to manufacturer’s instructions. For mature cell populations, CD34- cells were FACS purified according to the following immunophenotypes, with 7-AAD used to exclude dead cells: Neutrophils: side scatter high CD15+ CD16+. Monocytes: side scatter low-intermediate CD14+ CD16- CD15-. See also Huang et al., 2014.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66254 | GEO | 2015/09/17

SECONDARY ACCESSION(S): PRJNA276269

REPOSITORIES: GEO

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Project description:The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel hematopoietic progenitors, including SSCloCD66b+CD15+CD11b-CD49dhiproNeu1s and SSChiCD66b+CD15+CD11b-CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101-preNeus and Lin-CD66b+CD117+CD71+eNePs along human neutropoiesis process. In this research field, we recently identified CD66b-CD38+CD64dimCD115-, CD34+ and CD34dim/-cells exclusively committed to the neutrophil lineage [which we renamed as CD34+ and CD34dim/- neutrophil-committed progenitors (NCPs)], representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify four populations of NCPs, namely: CD34+CD45RA-/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/-CD45RA+/NCP3s and CD34dim/-CD45RA-/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors termed either neutrophil progenitors (NePs) or “early neutrophil-committed progenitors” would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16-monocytes. Hence, presuming that NePs/alias “early neutrophil-committed progenitors” correspond to NCPs, the selective neutrophil-commitment that we attributed to NCPs is contradicted by Ikeda and coworkers’ paper. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by NCP2s and NCP4s (selected as representatives of NCPs), we categorically exclude that NCPs generate neutrophil-like CXCR1+CD14+CD16-monocytes. Rather, we provide substantial evidence indicating that the cells generated by NePs/alias “early neutrophil-committed progenitors” are neutrophilic cells at different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16-monocytes as pointed by Ikeda and coworkers. Hence, the conclusion that NePs/alias “early neutrophil-committed progenitors” aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation

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Frequent derepression of the mesenchymal transcription factor gene in acute myeloid leukemia (human)

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