Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: overactivated WNT/β-catenin signalling by parallel RNA sequencing and dysfunctional phenotypes
Correction(s) for this article
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Erratum to: Bone marrow mesenchymal stromal cells in chronic myelomonocytic leukaemia: Overactivated WNT/β-catenin signalling by parallel RNA sequencing and dysfunctional phenotypes
- Volume 201Issue 4British Journal of Haematology
- pages: 797-797
- First Published online: March 17, 2023
Ruohao Xu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Ruohao Xu and Xin Huang contributed equally to this article.
Search for more papers by this authorXin Huang
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Ruohao Xu and Xin Huang contributed equally to this article.
Search for more papers by this authorChao Li
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorChengxin Deng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorMinming Li
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorPing Wu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorSuxia Geng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorPeilong Lai
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorZesheng Lu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorCorresponding Author
Jianyu Weng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Correspondence: Jianyu Weng M.D., Ph.D. and Xin Du M.D., Ph.D., Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xin Du
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Correspondence: Jianyu Weng M.D., Ph.D. and Xin Du M.D., Ph.D., Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorRuohao Xu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Ruohao Xu and Xin Huang contributed equally to this article.
Search for more papers by this authorXin Huang
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Ruohao Xu and Xin Huang contributed equally to this article.
Search for more papers by this authorChao Li
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorChengxin Deng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorMinming Li
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorPing Wu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorSuxia Geng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorPeilong Lai
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorZesheng Lu
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Search for more papers by this authorCorresponding Author
Jianyu Weng
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Correspondence: Jianyu Weng M.D., Ph.D. and Xin Du M.D., Ph.D., Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xin Du
Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080 P.R. China
Correspondence: Jianyu Weng M.D., Ph.D. and Xin Du M.D., Ph.D., Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510080, P.R. China.
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorSummary
Sophisticated cross-talk between bone marrow mesenchymal stromal cells (BM MSCs) and haematopoietic/leukaemic stem cells in patients with myelodysplastic syndromes (MDS) and myeloid leukaemia have been emphasized in previous reports. However, mesenchymal elements in patients with chronic myelomonocytic leukaemia (CMML) were poorly investigated. By utilizing a parallel RNA-sequencing method, we investigated the transcriptional profile and functional defects of primary BM MSCs from patients with CMML for the first time. Within a 24-patient cohort, transcriptional and functional analysis reveals a prominent enrichment of WNT/β-catenin signalling and multiple biology processes. Deregulated expression of WNT/β-catnin factors CTNNB1, CMYC, LEF1, and FRZB is associated with impaired proliferation, senescence phenotype, and abnormal secretion in CMML MSCs. The impaired ability to support healthy CD34+ haematopoietic stem and progenitor cells (HSPCs) correlates with activation of WNT/β-catenin signalling in CMML MSCs. Furthermore, we observed an association between WNT/β-catenin factors and treatment response to hypomethylating agents (HMAs) in a cohort of patients with MDS/myeloproliferative neoplasms (MPNs). Taken together, our study provides evidence for transcriptional and functional abnormalities in CMML MSCs, and suggests potential prognostic value of evaluating WNT/β-catenin signalling in patients with CMML.
Conflicts of interest
The authors declare no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| bjh17425-sup-0001-Supinfo.docxWord document, 472.1 KB |
Figure S1. Frequency of CD31+ endothelial cells in BM-MNCs and CFU-F formed by primary BM-MSCs (A) Frequency of DAPI-CD45-CD235ab-CD31+ endothelial cells in bone marrow from healthy donors and patients with CMML (BM donor =10, CMML =15) (P = 0.061). (B) Primary BM-MSCs were sorted as DAPI-/CD45-/CD235ab-/CD31-/CD146+/CD271+ cells from MD-CMML (n = 7) and MP-CMML (n = 7) and age-matched healthy donor (n = 6). Figure S2. Osteogenic capacity of low-/high- WNT CMML-MSCs (A) Osteogenic ability of BM-MSCs at passage 2-4. Mineralization was visualized with alizarin red and quantified photometrically at 560 nm in duplicates (HD-MSC=6, low WNT CMML-MSC=4, high WNT CMML-MSC=4). (B) Frequency of DAPI-CD45-CD235ab-CD31-Cadherin-11+ BM-OBCs in bone marrow non-hematopoietic subset (CD45-CD235ab-CD34-) from healthy donors and patients with CMML (BM donor =10, low WNT CMML =12, high WNT CMML=12). (C) FACS gating strategy to identify and isolate DAPI-/CD45-/CD235ab-/CD31-/Cadherin-11+ primary BM-OBCs. Table S1. Response to external stimuli and and cytokines by GSEA. Table S2. Baseline characteristics of CMML/MDS patients and BM donors. Table S3. Clinical outcomes of CMML patients. Table S4. Clinical outcomes of CMML patients with high-frequency mutations. Table S5. Primer sequences for qPCR. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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