Macrophage frequency in the bone marrow correlates with morphologic subtype of myeloproliferative neoplasm

Annals of Hematology, vol. 100, pp. 97–104

Abstract

Bone marrow (BM) fibrosis in myeloproliferative neoplasms (MPNs) is associated with a poor prognosis. The development of myelofibrosis and differentiation of mesenchymal stromal cells to profibrotic myofibroblasts depends on macrophages. Here, we compared macrophage frequencies in BM biopsies of MPN patients and controls (patients with non-neoplastic processes), including primary myelofibrosis (PMF, n = 18), essential thrombocythemia (ET, n = 14), polycythemia vera (PV, n = 12), and Philadelphia chromosome-positive chronic myeloid leukemia (CML, n = 9). In PMF, CD68-positive macrophages were greatly increased compared to CML (p = 0.017) and control BM (p < 0.001). Similar findings were observed by CD163 staining (PMF vs. CML: p = 0.017; PMF vs. control: p < 0.001). Moreover, CD68-positive macrophages were increased in PV compared with ET (p = 0.009) and reactive cases (p < 0.001). PMF had higher frequencies of macrophages than PV (CD68: p < 0.001; CD163: p < 0.001) and ET (CD68: p < 0.001; CD163: p < 0.001). CD163 and CD68 were often co-expressed in macrophages with stellate morphology in Philadelphia chromosome-negative MPN, resulting in a sponge-like reticular network that may be a key regulator of unbalanced hematopoiesis in the BM space and may explain differences in cellularity and clinical course.

Authors 9

1. David C. A. Molitor

   University Hospital Bonn

   Affiliation as printed

   Institute of Pathology, University Hospital Bonn, Bonn, Germany

2. Peter Boor Aachen Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Pathology, University Hospital Aachen, RWTH Aachen, Bonn, Germany

3. Andreas Buneß

   University of Bonn · Institut für Medizinische Biometrie, Informatik und Epidemiologie

   Affiliation as printed

   Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany

   Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany

4. Rebekka K. Schneider Aachen Institute for Biomedical Engineering Department of Cell Biology

   Erasmus MC · Erasmus MC Cancer Institute · RWTH Aachen University

   Affiliation as printed

   Department of Hematology, Erasmus MC Cancer Center, Rotterdam, Netherlands

   Institute for Biomedical Engineering Department of Cell Biology , RWTH , Aachen, Germany

5. Lino Lars Teichmann

   University Hospital Bonn

   Affiliation as printed

   Department of Hematology and Oncology, University Hospital Bonn, Bonn, Germany

6. Ruth-Miriam Körber

   University Hospital Bonn

   Affiliation as printed

   Department of Hematology and Oncology, University Hospital Bonn, Bonn, Germany

7. Gabor L Horvath

   University of Bonn

   Affiliation as printed

   Medical Faculty, Microscopy Core Facility, University of Bonn, Bonn, Germany

8. Steffen Koschmieder Aachen Department of Hematology, Oncology Faculty of Medicine

   RWTH Aachen University

   Affiliation as printed

   Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen, Aachen, Germany

9. Ines Gütgemann corresponding

   University Hospital Bonn

   Affiliation as printed

   Institute of Pathology, University Hospital Bonn, Bonn, Germany. Ines.Guetgemann@ukbonn.de

   Institute of Pathology, University Hospital Bonn, Bonn, Germany