Recipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.

Multi-niche human bone marrow on-a-chip for studying the interactions of adoptive CAR-T cell therapies with multiple myeloma.

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.

Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports hint at a role for signal transducer and activator of transcription (STAT) 6 signaling in non-immune cells, the contribution of STAT6-activation particularly in intestinal epithelial cells (IECs) is still unknown. Dextran sodium sulfate (DSS)-induced colitis is a model for UC in mice that we applied here on animals with expression of a constitutively active version of STAT6 in IECs (VillinCre_STAT6vt mice).

Plasma pTau217 ratio predicts continuous regional brain tau accumulation in amyloid-positive early Alzheimer's disease.

Background: This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD).

Methods: Plasma pTau217R was measured using immunoprecipitation-mass spectrometry. Models for predicting tau PET SUVR, developed with 144 early AD individuals using [F]MK6240, were validated in two validation sets, VS1 (98 early AD) and VS2 (47 preclinical/early AD with a different tracer, flortaucipir (Tauvid)), all amyloid-beta positive (Aβ+).