A circulating subset of BRAFV600E -positive cells in infants with high-risk Langerhans cell histiocytosis treated with BRAF inhibitors.

BRAF inhibitors are an effective treatment for BRAFV600E -mutated, risk-organ-positive Langerhans cell histiocytosis (RO+ LCH). However, cell-free BRAFV600E DNA often persists during therapy and recurrence frequently occurs after therapy discontinuation. To identify a pathological reservoir of BRAFV600E -mutated cells, we studied peripheral blood cells obtained from six infants with RO+ multisystem (MS) LCH that received targeted therapy. After cell sorting, the BRAFV600E mutation was detected in monocytes (n = 5), B lymphocytes (n = 3), T lymphocytes (n = 2), and myeloid and plasmacytoid dendritic cells (n = 2 each). This biomarker may offer an interesting tool for monitoring the effectiveness of new therapeutic approaches for weaning children with RO+ LCH from targeted therapy.

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. RESULTS: Here we show that symptomatic maternal COVID-19 is associated with a transcriptional erythroid cell signature as compared with asymptomatic and uninfected mothers. We observe an expansion of fetal hematopoietic multipotent progenitors skewed towards erythroid differentiation that display increased clonogenicity. There was no difference in inflammatory cytokines levels in the cord blood upon maternal SARS-CoV-2 infection. Interestingly, we show an activation of hypoxia pathway in cord blood cells from symptomatic COVID-19 mothers, suggesting that maternal hypoxia may be triggering this fetal stress hematopoiesis. CONCLUSIONS: Overall, these results show a fetal hematopoietic response to symptomatic COVID-19 in pregnant mothers in the absence of vertically transmitted SARS-CoV-2 infection which is likely to be a mechanism of fetal adaptation to the maternal infection and reduced oxygen supply.

During pregnancy, women are more prone to respiratory infectious diseases. It is not known if COVID-19 infection has an adverse effect on the growing fetus. Here, we aimed to identify any potential effects of COVID-19 infection on the fetus by taking measurements from the umbilical cord blood cells. In mothers who displayed symptomatic COVID-19 infection, we observed an increased production of hematopoietic progenitor cells, especially the ones that are responsible for producing red blood cells. We think this might be a coping mechanism for the fetus, as the mother's body deals with the infection. Therefore, our work shows that growing fetuses do respond to maternal COVID-19 symptoms, even when they are protected in the womb from the infection and may never get infected by the mother.