Inflammatory profile of lower risk myelodysplastic syndromes.

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs).

Lymphoid blood cancers, incidence and survival 2005-2023: A report from the UK's Haematological Malignancy Research Network.

Background: Population-based information on cancer incidence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many lymphoid cancer subtypes.

Methods: Set within a socio-demographically representative UK population of ∼4 million, data are from an established UK patient cohort (N = 22,414 diagnoses). Information on incidence (crude and age-standardised) and survival (overall and net) is presented for > 40 subtypes.

Multiparameter prediction of myeloid neoplasia risk.

The myeloid neoplasms encompass acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Most cases arise from the shared ancestor of clonal hematopoiesis (CH). Here we analyze data from 454,340 UK Biobank participants, of whom 1,808 developed a myeloid neoplasm 0-15 years after recruitment.

Phase Ib study of eltrombopag and azacitidine in patients with high-risk myelodysplastic syndromes and related disorders (the ELASTIC study).

Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 10 /l received eltrombopag ranging from 25 to 300 mg.

Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.

Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors.

Novel somatic mutations in UBA1 as a cause of VEXAS syndrome.

Poulter and colleagues describe a series from the United Kingdom of 10 male patients with VEXAS syndrome, including 2 with novel genetic changes affecting methionine 41 of E1.

Somatic Mutations and the Risk of Undifferentiated Autoinflammatory Disease in MDS: An Under-Recognized but Prognostically Important Complication.

We theorized that myelodysplastic syndrome (MDS) with somatic mutations and karyotype abnormalities are associated with autoinflammation, and that the presence of autoinflammatory disease affected prognosis in MDS. One hundred thirty-four MDS patients were assessed for the prevalence of autoinflammatory complications and its link with karyotypes and somatic mutation status. Autoinflammatory complications were described either as well-defined autoinflammatory diseases (AD) or undifferentiated "autoinflammatory disease" (UAD) (defined as CRP over 10.