Myeloid sarcoma is a rare disease that can present as an isolated extramedullary leukemic tumor, concurrently with or at relapse of acute myeloid leukemia. Owing to the rarity of this disorder, most of the literature comprises small retrospective studies and case reports. The aim of this review is to summarize the current published data regarding the clinical presentation, morphological, cytogenetic and molecular features, prognosis and treatment of myeloid sarcoma.

Background: Bone marrow mesenchymal stem cells (bmMSC) may play a role in the regulation of maturation, proliferation, and functional activation of lymphocytes, though the exact mechanisms are unknown. MSC-derived exosomes induce a regulatory response in the function of B, T, and monocyte-derived dendritic cells. Here, we evaluated the specific inhibition of human lymphocytes by bmMSC-derived exosomes and the effects on B-cell function. Methods: Exosomes were isolated from culture media of bmMSC obtained from several healthy donors. The effect of purified bmMSC-derived exosomes on activated peripheral blood mononuclear cells (PBMCs) and isolated B and T lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester assay. Using the Illumina sequencing platform, mRNA profiling was performed on B-lymphocytes activated in the presence or absence of exosomes. Ingenuity^® pathway analysis software was applied to analyze pathway networks, and biological functions of the differentially expressed genes. Validation by RT-PCR was performed. The effect of bmMSC-derived exosomes on antibody secretion was measured by ELISA. Results: Proliferation of activated PBMCs or isolated T and B cells co-cultured with MSC-derived exosomes decreased by 37, 23, and 18%, respectively, compared to controls. mRNA profiling of activated B-lymphocytes revealed 186 genes that were differentially expressed between exosome-treated and control cells. We observed down- and up-regulation of genes that are involved in cell trafficking, development, hemostasis, and immune cell function. RNA-Seq results were validated by real time PCR analysis for the expression of CXCL8 (IL8) and MZB1 genes that are known to have an important role in immune modulation. Functional alterations were confirmed by decreased IgM production levels. Consistent results were demonstrated among a wide variety of healthy human bmMSC donors. Conclusion: Our data show that exosomes may play an important role in immune regulation. They inhibit proliferation of several types of immune cells. In B-lymphocytes they modulate cell function by exerting differential expression of the mRNA of relevant genes. The results of this study help elucidate the mechanisms by which exosomes induce immune regulation and may contribute to the development of newer and safer therapeutic strategies.

Early detection of relapsed lymphoma improves response and survival. Current tools lack power for detection of early relapse, while being cumbersome and expensive. We searched for sensitive biomarkers that precede clinical relapse, and serve for further studies on therapy response and relapse. We recruited 20 healthy adults, 14 diffuse large B-cell lymphoma (DLBCL) patients and 11 Hodgkin lymphoma (HL) patients at diagnosis. Using small-RNA sequencing we identified in DLBCL patients increased plasma levels of miR-124 and miR-532-5p, and decreased levels of miR-425, miR-141, miR-145, miR-197, miR-345, miR-424, miR-128 and miR-122. In the HL group, we identified miR-25, miR-30a/d, miR-26b, miR-182, miR-186, miR-140* and miR-125a to be up-regulated, while miR-23a, miR-122, miR-93 and miR-144 were down-regulated. Pathway analysis of potential mRNAs targets of these miRNA revealed in the DLBCL group potential up-regulation of STAT3, IL8, p13k/AKT and TGF-B signaling, and potential down-regulation of the PTEN and p53 pathways; while in the HL group we have found the cAMP-mediated pathway and p53 pathway to be potentially down-regulated. Survival analyses revealed that plasma levels of miR-20a/b, miR-93 and miR-106a/b were associated with higher mortality. In conclusion, we identified sets of dysregulated circulating miRNA that might serve as reliable biomarkers for relapsed lymphoma.

The objective of this study was to examine whether aortic stiffness, as assessed by pulse wave analysis, could reliably discriminate between normal and hypertensive pregnancies. One hundred pregnant women were studied: five with severe pre-eclampsia, 27 with gestational hypertension, 14 with chronic hypertension and 54 with normal pregnancy. Central hemodynamic parameters were obtained by an applanation tonometry and included central aortic systolic blood pressure (CSBP), central aortic diastolic blood pressure (CDBP), augmentation pressure (AP), augmentation index (AIx), AIx corrected to a heart rate of 75 (AIx@75) and time to reflection (Tr). All measures of aortic stiffness, including AP, AIx and AIx@75 were significantly higher in women with gestational hypertension and pre-eclampsia compared with normal pregnancies and women with chronic hypertension (p < 0.05 for all comparisons). There were no significant differences between normal pregnancies and women with chronic hypertension (p > 0.05 for all comparisons). Tr was significantly shorter in women with pre-eclampsia and gestational hypertension compared with normal pregnancies (p < 0.05). Aortic stiffness, as assessed by pulse wave analysis, is significantly increased in women with pre-eclampsia and gestational hypertension but not in treated women with chronic hypertension. Pulse wave analysis has a potential as a screening tool in women at high risk for pre-eclampsia. The final role of this method should be determined in prospective studies.

Significance: The clinical utility of mesenchymal stromal/stem cells (MSCs) in mediating immunosuppressive effects and supporting regenerative processes is broadly established. However, the inherent heterogeneity of MSCs compromises its biomedical efficacy and reproducibility. To study how cellular variation affects fate decision-making processes, we perform single-cell RNA sequencing at multiple time points during bipotential matrix-directed differentiation toward soft- and stiff tissue lineages. In this manner, we identify distinctive MSC subpopulations that are characterized by their multipotent differentiation capacity and mechanosensitivity. Also, whole-genome screening highlights TPM1 as a potent mechanotransducer of matrix signals and regulator of cell differentiation. Thus, by introducing single-cell methodologies into mechanobiology, we delineate the complexity of adult stem cell responses to extracellular cues in tissue regeneration and immunomodulation.