IPSS-M risk and specific sex-associated somatic mutations predict response to ESA therapy in LR-MDS: building a new score.

Acquired somatic mutations are incorporated in the classification and prognosis of myelodysplastic syndromes/neoplasms (MDS). However, the predictive role of molecular features in MDS need to be elucidated, especially in the lower-risk subtypes (LR-MDS), where treatment has become more heterogenous, and specific predictive biomarkers are lacking. In this study we investigated genetic markers associated with erythropoiesis stimulating agent (ESA) response in LR-MDS.

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS.

Loss of hematopoietic progenitors heterogeneity is an adverse prognostic factor in lower-risk myelodysplastic neoplasms.

Myelodysplastic neoplasms (MDS) are characterized by clonal evolution starting from the compartment of hematopoietic stem and progenitors cells (HSPCs), leading in some cases to leukemic transformation. We hypothesized that deciphering the diversity of the HSPCs compartment may allow for the early detection of an emergent sub-clone that drives disease progression. Deep analysis of HSPCs repartition by multiparametric flow cytometry revealed a strong disorder of the hematopoietic branching system in most patients at diagnosis with different phenotypic signatures closely related to specific MDS features.

White blood cells scattergram as a valuable tool for COVID-19 screening: A multicentric study.

Introduction: New tools have been developed to distinguish the COVID-19 diagnosis from other viral infections presenting similar symptomatology and mitigate the lack of sensitivity of molecular testing. We previously identified a specific "sandglass" aspect on the white blood cells (WBC) scattergram of COVID-19 patients, as a highly reliable COVID-19 screening test (sensitivity: 85.9%, specificity: 83.

Enhanced fetal hematopoiesis in response to symptomatic SARS-CoV-2 infection during pregnancy.

Background: Pregnant women and their fetuses are particularly susceptible to respiratory pathogens. How they respond to SARS-CoV-2 infection is still under investigation.

Methods: We studied the transcriptome and phenotype of umbilical cord blood cells in pregnant women infected or not with SARS-CoV-2.

Neutralizing Antibody Levels as a Correlate of Protection Against SARS-CoV-2 Infection: A Modeling Analysis.

Although anti-severe acute respiratory syndrome-coronavirus 2 antibody kinetics have been described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and how this impacts viral clearance. For that purpose, we analyzed the kinetics of both viral load and neutralizing antibody levels in a prospective cohort of individuals during acute infection with alpha variant. Using a mathematical model, we show that the progressive increase in neutralizing antibodies leads to a shortening of the half-life of both infected cells and infectious viral particles.

[Pathophysiology of myelodysplastic syndromes].

During aging, the onset of mutations at low frequency in hematopoietic cells or clonal hematopoiesis of indeterminate significance favors the evolution towards hemopathies such as myelodysplastic syndromes or acute leukemias, but also cardiovascular diseases and other pathologies. Acute or chronic inflammation related to age influences the clonal evolution and the immune response. Conversely, mutated hematopoietic cells create an inflammatory bone marrow environment facilitating their expansion.

Artificial intelligence to empower diagnosis of myelodysplastic syndromes by multiparametric flow cytometry.

The diagnosis of myelodysplastic syndromes (MDS) might be challenging and relies on the convergence of cytological, cytogenetic, and molecular factors. Multiparametric flow cytometry (MFC) helps diagnose MDS, especially when other features do not contribute to the decision-making process, but its usefulness remains underestimated, mostly due to a lack of standardization of cytometers. We present here an innovative model integrating artificial intelligence (AI) with MFC to improve the diagnosis and the classification of MDS.

Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group.

Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS.

Plasma Endocan as a Biomarker of Thrombotic Events in COVID-19 Patients.

(1) Background: Endocan is a marker of endothelial dysfunction that may be associated with thrombotic events. The aim of the study was to investigate the performance of endocan as a marker of thrombotic events in COVID-19 patients. (2) Methods: We measured endocan in plasma from 79 documented COVID-19 patients classified according to disease severity (from mild to critical).

Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications.

Myelodysplastic syndromes (MDS) constitute a very heterogeneous group of diseases with a high prevalence in elderly patients and a propensity for progression to acute myeloid leukemia. The complexity of these hematopoietic malignancies is revealed by the multiple recurrent somatic mutations involved in MDS pathogenesis and the paradoxical common phenotype observed in these patients characterized by ineffective hematopoiesis and cytopenia. In the context of population aging, the incidence of MDS will strongly increase in the future.

Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

Background: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated.

Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group.

This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients.