Leptin Receptor + (LepR + ) stromal cells in adult bone marrow are a critical source of growth factors, including Stem Cell Factor (SCF), for the maintenance of hematopoietic stem cells (HSCs) and early restricted progenitors 1 – 6 . LepR + cells are heterogeneous, including skeletal stem cells, osteogenic, and adipogenic progenitors 7 – 12 , though few markers have been available to distinguish these subsets or to compare their functions. Here we show expression of an osteogenic growth factor, Osteolectin 13 , 14 , distinguishes peri-arteriolar LepR + cells poised to undergo osteogenesis from peri-sinusoidal LepR + cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LepR + Osteolectin + cells are rapidly dividing, short-lived, osteogenic progenitors that increase in number after fracture and are depleted during aging. Deletion of Scf from adult Osteolectin + cells did not affect the maintenance of HSCs or most restricted progenitors but depleted common lymphoid progenitors (CLPs), impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar Osteolectin + cell maintenance required mechanical stimulation. Voluntary running increased, while hindlimb unloading decreased, the frequencies of peri-arteriolar Osteolectin + cells and CLPs. Deletion of the mechanosensitive ion channel, Piezo1 , from Osteolectin + cells depleted Osteolectin + cells and CLPs. A peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during aging.

Studies of genetic blood disorders have advanced our understanding of the intrinsic regulation of hematopoiesis. However, such genetic studies have only yielded limited insights into how interactions between hematopoietic cells and their microenvironment are regulated. Here, we describe two affected siblings with infantile myelofibrosis and myeloproliferation that share a common de novo mutation in the Rho GTPase CDC42 (Chr1:22417990:C>T, p.R186C) due to paternal germline mosaicism. Functional studies using human cells and flies demonstrate that this CDC42 mutant has altered activity and thereby disrupts interactions between hematopoietic progenitors and key tissue microenvironmental factors. These findings suggest that further investigation of this and other related disorders may provide insights into how hematopoietic cell-microenvironment interactions play a role in human health and can be disrupted in disease. In addition, we suggest that deregulation of CDC42 may underlie more common blood disorders, such as primary myelofibrosis.

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Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders. We identified 10 cases of EBV MZL, 9 in extranodal sites and 1 presenting in lymph node. Two cases arose following solid organ transplantation, but other settings included iatrogenic immunosuppression for rheumatoid arthritis (2); prior chemotherapy (2); congenital immune deficiency (1); and increased age (3), as the only potential cause of immune dysfunction. There were 4 males and 6 females; age range 18 to 86. The atypical plasmacytoid and/or monocytoid B cells were positive for EBV in all cases, with either latency I or II in all cases tested. Monotypic light chain expression was shown in all with 6 cases positive for IgG, and 2 for IgM, undetermined in 2. Clonal immunoglobulin gene rearrangement was positive in all cases with successful amplification. MYD88 L265P was wild type in the 6 cases tested. We show that EBV MZLs can arise in a variety of clinical settings, and are most often extranodal. Treatment varied, but most patients had clinically indolent disease with response to reduction of immune suppression, or immunochemotherapy.

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Hematopathologists are witnessing very exciting times, as a new era of unsurpassed technological advances is unfolding exponentially, enhancing our understanding of diseases at the genomic and molecular levels. In the evolving field of precision medicine, our contributions as hematopathologists to medical practice are of paramount importance. Social media platforms such as Twitter have helped facilitate and enrich our professional interactions and collaborations with others in our field and in other medical disciplines leading to a more holistic approach to patient care. These platforms also have created a novel means for instantaneous dissemination of new findings and recent publications, and are proving to be increasingly useful tools that can be harnessed to expand our knowledge and amplify our presence in the medical community. In this Editorial, we share our experience as hematopathologists with Twitter, and how we leveraged this platform to boost scholarly activities within and beyond our subspecialty, and as a powerful medium for worldwide dissemination of educational material and to promote our remote teaching activities during the COVID-19 pandemic. Recent advances in technology have provided 21st century scholars with a plethora of tools to harness and remodel our skills and interests, and to optimize our career paths [1]. Social media have provided medical professionals with a novel platform for real-time interaction, education, patient engagement, collaborations, and networking [2]. Such applications, spanning the healthcare continuum, are further