Soluble HLA-G and HLA-E Levels in Bone Marrow Plasma Samples Are Related to Disease Stage in Neuroblastoma Patients

Fabio Morandi,Maria Valeria Corrias,Vito Pistoia,Loredana Amoroso,Sarah Pozzi,Barbara Carlini

doi:10.1155/2016/7465741

Fabio Morandi, Maria Valeria Corrias + Show 4 more

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https://doi.org/10.1155/2016/7465741

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Abstract

The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations. This hypothesis was supported by the finding that sHLA-G and sHLA-E levels did not correlate with BM infiltration and other adverse prognostic factors (MYCN amplification and age at diagnosis). In contrast, BM plasma levels of both molecules were higher in patients with metastatic disease than in patients with localized NB, thus suggesting that concentration of these molecules might be correlated with disease progression. The prognostic role of sHLA-G and sHLA-E concentration in the BM plasma for NB patients will be evaluated in future studies, by analyzing the clinical outcome of the same NB patients at follow-up.

Highlights

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of 1 case per 100.000 children per year, and causes 15% of cancer deaths in pediatric age
Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, suggesting that these molecules are physiologically released by resident or stromal BM cell populations
We demonstrated for the first time that sHLA-G and sHLA-E are present in BM plasma samples derived from either NB patients at diagnosis or healthy donors

Summary

Introduction

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of 1 case per 100.000 children per year, and causes 15% of cancer deaths in pediatric age. BM infiltration is an indicator of poor outcome for NB patients [2]. The International Neuroblastoma Risk Group staging system takes into account genetic alterations, DNA ploidy, histological features, and clinical data, as criteria for defining the risk classes. The prognosis of low/intermediate risk NB patients is favorable, and tumors can be cured by surgery alone or minimal chemotherapy. Highrisk NB patients’ prognosis is poor, in spite of aggressive treatment based on surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, and adjuvant therapy with retinoic acid. Survival rates of these patients at 5 years are less than 50% [3]

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