A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.

Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma.

Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients with advanced melanoma but is not limited to melanoma patients. Many patients are refractory to TIL-ACT, however, or their cancer becomes resistant.

Do Medical Graduates from a Rural Longitudinal Integrated Clerkship Work in Similar Rural Communities?

(1) Background: Medical graduates who have undertaken longitudinal rural training have consistently been found to be more likely to become rural doctors and work in primary care settings. A limitation of such findings is the heterogeneous nature of rural medical education and contested views of what constitutes 'rurality', especially as it is often reported as a binary concept (rural compared to metropolitan). To address the identified gaps in workforce outcomes for rural medical training and to demonstrate accountability to the communities we serve, we investigated whether Longitudinal Integrated Clerkship (LIC) graduates are practicing in communities with similar rural classification to those where they trained.

Donor C1 Group KIR-ligand inferiority is linked to increased mortality in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide.

Background Aims: In HLA-identical hematopoietic stem cell transplantation (HSCT), HLA-C1 group killer cell immunoglobulin-like receptor (KIR) ligands have been linked to graft-versus-host disease, whereas C2 homozygosity was associated with increased relapses. The differential impact of the recipients versus the donor's HLA-C KIR ligands cannot be determined in HLA-identical HSCT but may be elucidated in the haploidentical setting, in which HLA-C (including the HLA-C KIR ligand group) mismatching is frequently present.

Methods: We retrospectively investigated the effect of recipient versus donor C1 ligand content on survival and complications in post-transplant cyclophosphamide (PTCy)-based haploidentical HSCT (n = 170).

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.