Abnormalities diagnosed on routine blood work, such as mild neutropenia, anaemia, thrombocytopenia and relative lymphocytosis, often have obscure aetiologies. A series of 30 patients were evaluated for various unexplained haematological abnormalities between 1997 and 2005, and found to have circulating monoclonal T-cell large granular lymphocytes (T-LGL). These patients fit the diagnosis of T-cell clonopathy of unknown significance (TCUS), which may represent a clinical spectrum of clonal T-LGL proliferation. Our patients were characterised by a complete absence of severe neutropenia (<0.5 x 10(9)/l), absence of recurrent neutropenic infection (0%), negative rheumatoid serology (0%) and a low incidence of constitutional symptoms (20%). This overall asymptomatic clinical presentation appeared to be different from other previously reported series of TCUS or T-LGL leukaemia who typically had symptomatology and required treatment. Our series of 30 patients represented the benign end of the spectrum of clonal T-LGL proliferation, and might reflect diagnosis at earlier stages of the condition relative to other reported series. TCUS may be a heterogeneous and under-diagnosed condition. This study further broadens our understanding of the clinical and laboratory manifestations of indolent clonal T-cell proliferation, and raises our awareness of this condition. We suggest that TCUS should be considered in the diagnostic evaluation of unexplained haematological problems.
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http://dx.doi.org/10.1111/j.1365-2141.2006.06374.x | DOI Listing |
Blood
January 2025
University of Chicago, Chicago, Illinois, United States.
Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
We have demonstrated that the cellular protein M-Sec promotes the transmission of human T-cell leukemia virus type 1 (HTLV-1) in vitro and in vivo. Here, we show how HTLV-1 utilizes M-Sec for its efficient transmission. HTLV-1-infected CD4+ T cells expressed M-Sec at a higher level than uninfected CD4+ T cells.
View Article and Find Full Text PDFAllergy
January 2025
Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Background: IgE-mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood.
View Article and Find Full Text PDFUnlabelled: The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response (FBR) and fibrosis around medical implants is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via enterotoxigenic (ETBF) infection and implanted the synthetic polymer polycaprolactone (PCL) into a distal muscle injury.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
Adoptive T-cell transfer has revolutionized the treatment of hematological malignancies. However, this approach has had very limited success in treating solid tumors, largely due to inadequate infiltration of vascularly administered T cells at tumor sites. The shear-resistant interaction between endothelial E-selectin and its cognate ligand expressed on leukocytes, sialyl Lewis X (sLe), is an essential prerequisite for extravasation of circulating leukocytes.
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