Sex Differences in Gut Microbiota and Their Relation to Arterial Stiffness (MIVAS Study).

Background: Recent research highlights the potential role of sex-specific variations in cardiovascular disease. The gut microbiome has been shown to differ between the sexes in patients with cardiovascular risk factors.

Objectives: The main objective of this study is to analyze the differences between women and men in the relationship between gut microbiota and measures of arterial stiffness.

Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia.

Adult B-cell acute lymphoblastic leukemia (B-ALL) is characterized by genetic heterogeneity and a high relapse rate, affecting over 40% of adults. However, the mechanisms leading to relapse in adults are poorly understood. Forty-four adult B-ALL patients were studied at both diagnosis and relapse by next-generation sequencing (NGS).

Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications.

Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the clonal expansion of abnormal lymphoid precursors in bone marrow, which leads to alterations in the processes of cell differentiation and maturation as a consequence of genetic alterations. The integration of conventional methods, such as cytogenetics and immunophenotyping, and next-generation sequencing (NGS) has led to significant improvements at diagnosis and patient stratification; this has also allowed the discovery of several novel molecular entities with specific genetic variants that may drive the processes of leukemogenesis. Nevertheless, the understanding of the process of leukemogenesis remains a challenge since this disease persists as the most frequent cancer in children; it accounts for approximately one-quarter of adult acute leukemias, and the patient management may take into consideration the high intra- and inter-tumor heterogeneity and the relapse risk due to the various molecular events that can occur during clonal evolution.

Molecular profiling of pre- and post- 5-azacytidine myelodysplastic syndrome samples identifies predictors of response.

Treatment with the hypomethylating agent 5-azacytidine (AZA) increases survival in high-risk (HR) myelodysplastic syndrome (MDS) patients, but predicting patient response and overall survival remains challenging. To address these issues, we analyzed mutational and transcriptional profiles in CD34+ hematopoietic stem/progenitor cells (HSPCs) before and following AZA therapy in MDS patients. AZA treatment led to a greater reduction in the mutational burden in both blast and hematological responders than non-responders.

Low dose lenalidomide versus placebo in non-transfusion dependent patients with low risk, del(5q) myelodysplastic syndromes (SintraREV): a randomised, double-blind, phase 3 trial.

Background: Lenalidomide is the standard of care for patients who are transfusion dependent with chromosome 5q deletion (del[5q]) myelodysplastic syndromes. In the SintraREV trial, we aimed to investigate whether an early intervention of low lenalidomide doses for 2 years could delay transfusion dependency in patients with anaemia who were not transfusion dependent.

Methods: This randomised, double-blind, phase 3 trial, was conducted at 22 sites (University Hospitals) in Spain, France, and Germany.

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis.

Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

Background: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA).

Methods: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited.

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes.

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' survival dependence from BCL2-mediated anti-apoptotic pathways to TNFα-induced pro-survival NF-κB signaling and drives resistance to venetoclax-mediated cytotoxicity.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3 T-cells to engage and lyse CD19 target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.

The prognostic impact of non-driver gene mutations and variant allele frequency in primary myelofibrosis.

Prognostic impact of non-MPN driver gene mutations in primary myelofibrosis. MIPSS70: Mutation-Enhanced International Prognostic Score System.

Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes.

Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients.

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

Background: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients.

Aims: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice.

Methods: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment.

Mutational Profile Enables the Identification of a High-Risk Subgroup in Myelodysplastic Syndromes with Isolated Trisomy 8.

Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated with clinical heterogeneity and intermediate cytogenetic risk when found in isolation. The presence of gene mutations in this group of patients and the prognostic significance has not been extensively analyzed. Targeted deep sequencing was performed in a cohort of 79 MDS patients showing isolated +8.

Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.

Background: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function.

Results of the compassionate program of inotuzumab ozogamicin for adult patients with relapsed or refractory acute lymphoblastic leukemia in Spain.

Introduction: The prognosis of relapsed B cell precursor acute lymphoblastic leukemia (B-ALL) is poor and few patients can be successfully rescued with conventional therapies. Inotuzumab ozogamicin (IO), an antibody against the CD22 antigen linked to calicheamicin, has been approved as a rescue treatment in relapsed/refractory (R/R) B-ALL.

Patients And Methods: This was an observational, retrospective, multicenter study of adult patients included in the Spanish program of compassionate use of IO in centers from the PETHEMA group (Programa Español de Tratamientos en Hematología).

A t(4;13)(q21;q14) translocation in B-cell chronic lymphocytic leukemia causing concomitant homozygous DLEU2/miR15a/miR16-1 and heterozygous ARHGAP24 deletions.

13q14 deletion is the most recurrent chromosomal aberration reported in B-CLL, having a favorable prognostic significance when occurring as the sole cytogenetic alteration. However, its clinical outcome is also related to the deletion size and number of cells with the del(13)(q14) deletion. In 10% of cases, 13q14 deletion arises following a translocation event with multiple partner chromosomes, whose oncogenic impact has not been investigated so far due to the assumption of a possible role as a passenger mutation.

Machine Learning Improves Risk Stratification in Myelofibrosis: An Analysis of the Spanish Registry of Myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making.