Monitoring Mast Cell Populations in Waldenström’s Macroglobulinemia: A Xenotransplantation Study

Nikistratos Siskos,Alexandros Chadras,Chryssa Bekiari,Anastasia S Tsingotjidou,Theophilos Poutahidis,Rohit Jain

doi:10.14302/issn.2372-6601.jhor-19-3092

Abstract

Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized mainly by uncontrolled accrual of M- immunoglobulin, secreted by malignant lymphoplasmatic cells. Mast cells interacting with malignant B-cells play an important role at the manifestation of the disease. Utilizing a previous xenotransplantation mouse model, this study evaluates long-term implant viability and quantifies distinct bone marrow mast cell populations along with their dynamics in non-WM and WM human bone implants. Non-WM bone implants were obtained from the femoral head of adult humans undergoing hip arthroplasty or hemiarthroplasty, whereas WM human bone implants originated from bone biopsies obtained from the posterior iliac crest of patients with active WM. All bone particles were implanted intramuscularly in twenty-four NOD/SCID mice. Following 3, 4 or 8 months postoperatively, xenografts were removed and studied using special histological techniques to identify mature and immature mast cells. Xenografts survived up to 8 months after implantation presenting normal cytoarchitecture (non-WM) or high-grade neoplastic infiltration and microresorption (WM bone biopsies). Statistical analysis of mast cell populations showed significant elevation regarding time progression and bone marrow microenvironment, thus suggesting the possible influence of malignant cells to the mast cell population in WM. This study presents the extended survival of intramuscular implantation of human adult bone xenografts into NOD/SCID mice and provides additional information on the interaction between mast cells and malignant B-cells.

Highlights

Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by the uncontrolled accumulation of clonally related lymphoplasmacytic cells, which secrete M- immunoglobulin (IgM) [1,2,3]
This study presents the extended survival of intramuscular implantation of human adult bone xenografts into NOD/SCID mice and provides additional information on the interaction between mast cells and malignant B-cells
Our study introduces the implantation of human bone xenograft with WM and the subsequent IgM production implying the development of the disease into the immunodeficient mice

Summary

Introduction

Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by the uncontrolled accumulation (predominantly in the bone marrow) of clonally related lymphoplasmacytic cells, which secrete M- immunoglobulin (IgM) [1,2,3]. Gender and ethnicity are factors that influence the development of the disease, with older males of Caucasian descent to be the group of people that are more affected by it. Males are twice more likely to develop WM than females and the incidence on Caucasians has increased the past two decades [4, 5]. Waldenström Macroglobulinemia clinical manifestations are attributed either to the infiltration of the bone marrow (and other extramedullary sites), or to the elevated IgM serum levels [6, 7]. Despite progression in disease understanding, WM treatment remains symptom-oriented, while factors like patient’s age and possible complications strongly influence the therapeutic protocol [6]. Our study introduces the implantation of human bone xenograft with WM and the subsequent IgM production implying the development of the disease into the immunodeficient mice

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Conclusion