A specific bone marrow cytokine pattern in de novo acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic cancers. Cytokines play an important role in the regulation of normal and pathologic hematopoiesis. A pro-inflammatory state, described in hematopoietic malignancies, may participate in clonal selection.

Expanding the phenotypic and genetic landscape of congenital neutropenia through whole-exome and genome sequencing.

Congenital neutropenia (CN) comprises a heterogeneous group of rare genetic disorders. While some CN cases present only with neutropenia, others present with additional extra-hematological manifestations. The most common cause of CN is variants in ; however, approximately 30 other genes have been implicated.

Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group.

VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome is a severe monogenic disorder caused by somatic UBA1 mutations, characterized by inflammation, cytopenias and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential in VEXAS but data remain limited.

IgA vasculitis associated with chronic myelomonocytic leukemia.

IgA vasculitis is a predominantly pediatric autoimmune disease characterized by IgA deposit in small vessels. Chronic myelomonocytic leukemia (CMML) is a rare hematological malignancy classified within myelodysplastic syndromes. Here, we present a previously unrecognized case of CMML associated with IgA vasculitis.

[VEXAS-like auto inflammatory syndrome: 2 cases].

Introduction: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), recently described, due to a somatic mutation of the UBA1 gene and often associated with hemopathy, is characterized by systemic symptoms close to those described in Still's disease or relapsing polychondritis. There are also patients with hemopathy, presenting inflammatory symptoms reminiscent of those of VEXAS syndrome but without mutation of the UBA1 gene.

Case/discussion: Two male patients consulted for general signs, dermatological symptoms, arthralgia, chondritis and venous thrombosis, like patients in the French cohort suffering from VEXAS syndrome.

Long-term assessment of haematological recovery following somatic genetic rescue in a MYSM1-deficient patient: Implications for in vivo gene therapy.

MYSM1 deficiency causes inherited bone marrow failure syndrome (IBMFS). We have previously identified an IBMFS patient with a homozygous pathogenic variant in MYSM1 who recovered from cytopenia due to spontaneous correction of one MYSM1 variant in the haematopoietic compartment, an event called somatic genetic rescue (SGR). The study of the genetic and biological aspects of the patient's haematopoietic/lymphopoietic system over a decade after SGR shows that one genetically corrected haematopoietic stem cell (HSC) can restore a healthy and stable haematopoietic system.

Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: An ALFA study.

The evaluation of measurable residual disease (MRD) in acute myeloid leukemia (AML) using comprehensive mutation analysis by next-generation sequencing (NGS) has been investigated in several studies. However controversial results exist regarding the detection of persisting mutations in DNMT3A, TET2, and ASXL1 (DTA). Benchmarking of NGS-MRD taking into account other molecular MRD strategies has to be done.

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies.

Methods: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy.

JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development and complications remains unknown. In a cohort of patients with myeloproliferative neoplasm, JAK2V617F mutation was identified as an independent risk factor for dilation of both the ascending and descending thoracic aorta. Using single-cell RNA-seq, complementary genetically-modified mouse models, as well as pharmacological approaches, we found that JAK2V617F mutation was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages, and dissecting aneurysm through the recruitment of circulating monocytes at later stages.

Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia.

Chemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown.