Genocopy of EVI1-AML with paraneoplastic diabetes insipidus: PRDM16 overexpression by t(1;2)(p36;p21) and enhancer hijacking.

Diabetes insipidus (DI) in patients with acute myeloid leukaemia (AML) and chromosome 3q alterations (EVI1/PRDM3/MECOM overexpression) constitutes a poorly understood paraneoplasia. A 44-year-old patient presented with clinical and morphological features of this syndrome but, surprisingly, disclosed the rare translocation t(1;2)(p36;p21), with massive PRDM16 overexpression. WGS and RNA sequencing suggest enhancer hijacking of the ZFP36L2 enhancer region as underlying mechanism.

Immunological reconstitution and infections after alloHCT - a comparison between post-transplantation cyclophosphamide, ATLG and non-ATLG based GvHD prophylaxis.

Immunological reconstitution after allogeneic hematopoietic cell transplantation (alloHCT) is critical for patient survival. We compared short- and long-term immune reconstitution and clinical endpoints in adult recipients of haploidentical or mismatched T cell replete peripheral blood stem cell transplants (PBSCT) with post-transplant cyclophosphamide as GvHD prophylaxis (PTCY, n = 68) to: (a) patients receiving matched unrelated grafts and anti-T lymphocyte globulin (ATLG) (MUD/ATLG, n = 280); (b) patients with a mismatched donor and ATLG (MM/ATLG, n = 54); and (c) recipients of matched related grafts without ATLG (MRD/NoATLG, n = 97). PTCY was associated with delayed neutrophil engraftment, low NK-cell counts on day 30 and reduced CD8+ cells on days 60-80.

Evaluation of risk for bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation with myeloablative conditioning regimens.

Bronchiolitis obliterans syndrome (BOS), as chronic manifestation of graft-versus-host disease (GVHD), is a debilitating complication leading to lung function deterioration in patients after allogeneic hematopoietic cell transplantation (allo-HCT). In the present study, we evaluated BOS development risk in patients after receiving myeloablative conditioning (MAC) regimens. We performed a retrospective analysis of patients undergoing allo-HCT, who received MAC with busulfan/cyclophosphamid (BuCy, n = 175) busulfan/fludarabin (FluBu4, n = 29) or thiotepa/busulfan/fludarabine (TBF MAC, n = 37).

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase.

Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells.

Invariant natural killer T cells are a rare, heterogeneous T-cell subset with cytotoxic and immunomodulatory properties. During thymic development, murine invariant natural killer T cells go through different maturation stages differentiating into distinct sublineages, namely, invariant natural killer T1, 2, and 17 cells. Recent reports indicate that invariant natural killer T2 cells display immature properties and give rise to other subsets, whereas invariant natural killer T1 cells seem to be terminally differentiated.