Oncotarget

Research Papers:

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma

Fabio Morandi _, Sebastiano Barco, Sara Stigliani, Michela Croce, Luca Persico, Corrado Lagazio, Francesca Scuderi, Maria Luisa Belli, Mariapina Montera, Giuliana Cangemi, Sarah Pozzi, Valentina Rigo, Paola Scaruffi, Loredana Amoroso, Giovanni Erminio, Vito Pistoia, Silvano Ferrini and Maria Valeria Corrias

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Oncotarget. 2017; 8:53194-53209. https://doi.org/10.18632/oncotarget.18285

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Abstract

Fabio Morandi1, Sebastiano Barco2, Sara Stigliani3, Michela Croce4, Luca Persico5, Corrado Lagazio5, Francesca Scuderi6, Maria Luisa Belli6, Mariapina Montera7, Giuliana Cangemi2, Sarah Pozzi8, Valentina Rigo4, Paola Scaruffi3, Loredana Amoroso6, Giovanni Erminio9, Vito Pistoia10, Silvano Ferrini4 and Maria Valeria Corrias1

1UOC Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy

2UOC Clinical Pathology Laboratory, IRCCS Istituto Giannina Gaslini, Genoa, Italy

3UOS Physiopathology of Human Reproduction, IRCCS AOU SanMartino-IST, Genoa, Italy

4UOC Biotherapy, IRCCS AOU SanMartino-IST, Genoa, Italy

5Department of Economy, University of Genoa, Genoa, Italy

6UOC Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy

7UOC Immune-Hematology and Transfusion Medicine, IRCCS Istituto Giannina Gaslini, Genoa, Italy

8UOC Immune-Hematology and Transfusion Medicine, IRCCS AOU SanMartino-IST, Genoa, Italy

9UOS Epidemiology, Biostatistics and Committees, IRCCS Istituto Giannina Gaslini, Genoa, Italy

10Immunology Area, IRCCS Bambino Gesù, Rome, Italy

Correspondence to:

Fabio Morandi, email: fabiomorandi@gaslini.org

Keywords: neuroblastoma, erythrocytes, bone marrow, survival, microenvironment

Received: February 14, 2017    Accepted: May 09, 2017    Published: May 30, 2017

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.


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