Dataset Information

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma.

ABSTRACT: Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages' maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cytometry analysis. Gene ontology and disease-associated analysis of the genes significantly under-expressed in BM resident cells from children with localized and metastatic NB, as compared to healthy children, indicated anemia, blood group antigens, and heme and porphyrin biosynthesis as major functional annotation clusters. Accordingly, in children with NB there was a selective impairment of erythrocyte maturation at the ortho-chromic stage that resulted in reduced erythrocyte count in the periphery, regardless of the presence of metastatic cells in the BM. By considering all NB patients, low erythrocyte count at diagnosis associated with worse survival. Moreover, in the subset of metastatic patients, low erythrocyte count, hemoglobin and hematocrit and high red cell distribution width at follow-up also associated with worse outcome. These observations provide an alternative model to the tenet that infiltrating cells inhibit BM functions due to physical occupancy of space and may open a new area of research in NB to understand the mechanism(s) responsible for such selective impairment.

SUBMITTER: Morandi F

PROVIDER: S-EPMC5581103 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma.

Morandi Fabio F Barco Sebastiano S Stigliani Sara S Croce Michela M Persico Luca L Lagazio Corrado C Scuderi Francesca F Belli Maria Luisa ML Montera Mariapina M Cangemi Giuliana G Pozzi Sarah S Rigo Valentina V Scaruffi Paola P Amoroso Loredana L Erminio Giovanni G Pistoia Vito V Ferrini Silvano S Corrias Maria Valeria MV

Oncotarget 20170530 32

Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages' maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cy ...[more]

PMID: 28881804

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Project description:Neuroblastoma (NB) is a pediatric tumor with a heterogeneous presentation at diagnosis. Fifty per cent of patients present with localized disease (stage L1/L2) whereas the other half have metastatic disease (stage M), mainly involving the bone marrow (BM). In these latter patients the physical occupancy of the BM space by metastatic NB cells has been thought to be responsible for impairment of BM function. Here, based on gene expression profiles of BM resident cells obtained in a large number of stage L and stage M NB patients, as compared to gene expression profiles of BM resident cells from healthy subjects, we investigated whether the tumor growth, either at distance or locally, affected hematopoietic lineages' maturation and release of mature hematopoietic cells in the periphery (PB). Our investigation clearly demonstrated that in children with NB, regardless of the presence of metastatic cells in the BM, there was a selective impairment of erythrocyte maturation at the ortho-chromic stage. In the BM, all the other cell lineages were un-affected. The altered erythrocyte maturation resulted in a reduced amount, and increased RWD, of PB erythrocytes. In PB samples from patients with stage L disease a significant increase in the number of mature neutrophils was observed, suggesting that in these NB patients innate immunity was activated. No increase occurred in PB of stage M NB patients. Although the cause of the selective impairment of erythrocyte maturation, as well as that of the activation of innate immunity in stage L NB patients remained elusive, our observations allowed to fully refusing the tenet that BM-infiltrating NB cells affected physiological BM functions due to physical occupancy of the BM space. In addition, these findings open the way to a new area of research not only in NB and other clinically similar pediatric cancers, such as rhabdos and sarcomas, but also in adult cancers metastasizing in the BM. Looking more carefully to the BM microenvironment could help discovering novel targets for innovative therapeutic approaches.

Dataset Information

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma.

Publications

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma.

Similar Datasets

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