Prominence of nestin-expressing Schwann cells in bone marrow of patients with myelodysplastic syndromes with severe fibrosis
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Nestin-expressing stromal cells (NESCs) and Schwann cells in the bone marrow (BM) play crucial roles as a niche for normal hematopoietic stem cells in mice. It has been reported that both types of cells are decreased in myeloproliferative neoplasms in patients and also in a mouse model, whereas an increase in NESCs was reported in acute myeloid leukemia. It is thus of interest whether and how these BM stromal cells are structured in myelodysplastic syndromes (MDS). Here, we focused on NESCs and glial fibrillary acidic protein (GFAP)-expressing cells in the BM of MDS patients. We found a marked increase of NESCs in MDS with fibrosis (MDS-F) at a high frequency (9/19; 47.4%), but not in MDS without fibrosis (0/26; 0%). Intriguingly, in eight of the nine (88.9%) MDS-F cases with elevated NESCs, a majority of NESCs also expressed GFAP, with an additional increase in GFAP single-positive cells. Furthermore, in seven of them, we found a prominent structure characterized by neurofilament heavy chain staining surrounded by NESCs with GFAP expression. This structure may represent peripheral nerve axons surrounded by Schwann cells, and could be relevant to the pathophysiology of MDS-F.
KeywordsNestin-expressing stromal cells Schwann cells Myelodysplastic syndromes Fibrosis Human bone marrow
We thank Dr. Tran B. Nguyen and Dr. Xinh Thi Phan for their excellent discussion. We also thank Dr. Bryan J. Mathis and Ms. F. Miyamasu, Medical English Communications Center, University of Tsukuba, for their editorial assistance. We thank Prof. Masayuki Masu, Department of Molecular Neurobiology, University of Tsukuba, for providing anti-Tuj1 antibody. This work was supported by Grants-in-Aid for Scientific Research (Kakenhi Nos. 15K15359 (S.C.) and 17K09898 (N.O)) from the Ministry of Education, Culture, Sports, and Science of Japan; the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED) (S.C.); and Gilead Sciences International Research Scholars Program in Hematology/Oncology (H.N).
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Conflict of interest
The authors declare that they have no conflict of interest.
Patients’ samples are used in this work. All the patients provided written informed consent before inclusion in the study, and the study protocol was approved by the ethics committee of the University of Tsukuba Hospital, which adheres to the guidelines of the Declaration of Helsinki.