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Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis. Mice with stabilized β-catenin in BM-SEC (Ctnnb1) generated by using a BM-SEC-restricted Cre mouse line (Stab2-iCreF3) develop fatal anemia. While activation of Wnt-signaling in BM-SEC causes an increase in erythroblast subsets (PII-PIV), mature erythroid cells (PV) are reduced indicating impairment of terminal erythroid differentiation/reticulocyte maturation. Transplantation of Ctnnb1 hematopoietic stem cells into wildtype recipients confirms lethal anemia to be caused by cell-extrinsic, endothelial-mediated effects. Ctnnb1 BM-SEC reveal aberrant sinusoidal differentiation with altered EC gene expression and perisinusoidal ECM deposition and angiocrine dysregulation with de novo endothelial expression of FGF23 and DKK2, elevated in anemia and involved in vascular stabilization, respectively. Our study demonstrates that BM-SEC play an important role in the bone marrow microenvironment in health and disease.
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http://dx.doi.org/10.1038/s41467-021-27161-3 | DOI Listing |
Eur J Case Rep Intern Med
September 2025
Respiratory Department, University Hospital Limerick, Limerick, Ireland.
Unlabelled: B-cell lymphomas are highly aggressive forms of lymphoma that commonly present with lymphadenopathy, systemic "B" symptoms, or organ involvement making them easy to recognize; however, a small percentage of B-cell lymphomas can present without any typical symptoms or evidence of lymphadenopathy, resulting in delayed recognition and management. Isolated thrombocytopenia without anaemia or leukopenia is an unusual presentation of B cell lymphomas and may be misdiagnosed as immune thrombocytopenia (ITP). Given the rarity of this presentation, we wish to report a case of a 76-year-old female who presented with palpitations, shortness of breath, and recurrent chest infections.
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August 2025
Division of Hematology and Oncology, UNM Comprehensive Cancer Center, Albuquerque, USA.
Background: Blinatumomab and inotuzumab ozogamicin (InO) are B-cell targeted agents used in the frontline and relapsed/refractory treatment of B-cell acute lymphoblastic leukaemia (B-ALL). Blinatumomab, a bispecific T-cell engager that targets CD19 and CD3, and InO, an antibody-drug conjugate targeting CD22, have both shown efficacy. However, recent reports have noted lineage conversion as a complication when these agents are used individually or sequentially.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun, China.
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome that is caused primarily by immune-mediated destruction of hematopoietic stem cells. Traditional treatment relies on immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CSA). However, the toxicity and limited availability of ATG have spurred interest in ATG-free regimens.
View Article and Find Full Text PDFFront Immunol
September 2025
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
NSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34 hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown.
View Article and Find Full Text PDFFront Oncol
August 2025
Department Hematopathology, Shenzhen Hospital of Southern Medical University, Shenzhen, China.
Background: Mixed-phenotype acute leukemia (MPAL) is a rare acute leukemia for which data are currently not available to guide therapy. It has a poor outcome, particularly in elderly patients.
Case Presentation: We report the successful use of venetoclax/azacitidine as treatment for a treatment-naive elderly patient with early T-cell precursor (ETP)/myeloid MPAL.