Jesús M Hernández

• MD PhD
• Professor (Full) at University of Salamanca

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 m...

Introduction. The treatment of Ph-negative ALL is based on pediatric-inspired protocols that include allogeneic hematopoietic stem cell transplantation (alloHSCT) based on post-induction/consolidation measurable residual disease (MRD) and genetic characteristics. The PETHEMA LAL-2019 protocol (NCT 04179929) includes patients (pts) aged 18-60 yrs wi...

INTRODUCTION Acquired regions of homozygosity (aROHs) detected along the human genome are due to mitotic recombination between homologous chromosomes. This mechanism may contribute to the growth of a neoplastic clone if the involved region embraces tumor suppressor or onco-genes harbouring a mutation, with subsequent loss of the wild-type allele an...

Introduction Traditional risk stratification methods in Multiple Myeloma (MM) rely on clinical parameters and cytogenetic profiles, and often fall short in predictive accuracy. The advent of machine learning (ML) presents an opportunity to enhance risk prediction models by leveraging large datasets and complex variable interactions. Objectives The...

Introduction: β-thalassemia can be a severe transfusion-dependent disease, also called β-thalassemia major. There are heterozygous mild forms and intermediate forms. In recent years, there has been a clinical tendency to simplify the classification of symptomatic cases according to transfusion requirements into transfusion-dependent thalassemias (T...

Introduction. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a heterogeneous group of B-lineage ALL (B-ALL), accounting for 20-30% of adult cases and characterized by a gene expression profile similar to that of Ph+ ALL, lacking however the typical t(9;22)(q34;q11.2)/BCR::ABL1. The recurrent aberrations involve dysregulations of th...

Introduction. Young and middle-aged adults with ALL (18-60 years) who receive a pediatric-inspired chemotherapy (CHT) regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they had a negative MRD after induction therapy. It is not clear if the genetic risk at baseline associated with this MRD approach, would allow identifying...

Background FLT3-ITD mutations are found in approximately one quarter of patients with acute myeloid leukemia (AML). One major change in the 2022 ELN risk classification is the re-classification of all FLT3-ITD mutated patients as intermediate risk independently of allelic burden or NPM1 co-mutation. Recommendations state that FLT3-ITD mutations wit...

EKM, AM and MD contributed equally to this work. BACKGROUND. Despite major advances in the treatment of multiple myeloma (MM) in the past two decades, outcomes remain heterogenous, with some patients being primary refractory and others being long-term non-progressors. There is still an unmet need to identify patients at risk for early relapse/progr...

Background The Delphi technique is a well-known and accepted method to reach consensus. However, major challenges in Delphi studies include recruiting suitable participants and avoiding a loss of participants between survey rounds. To mitigate these challenges, we developed a virtual “Delphi hackathon” as a new method to conduct Delphi studies. We...

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. Objectives The objective w...

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...

Definition of a core outcome set (COS), which represents an agreed set of outcomes for each hematological malignancy (HM) may improve the interpretation and comparability of clinical trials. HARMONY – the Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology – and the follow up project HARMONY PLUS developed COS for...

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 a...

Trisomy 8 (+ 8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated to clinical heterogeneity and intermediate cytogenetic risk when found isolated. 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 coh...

Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated to clinical heterogeneity and intermediate cytogenetic risk when found isolated. 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 coho...

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1,...

B‐cell acute lymphoblastic leukemia (B‐ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B‐ALL. Although hyperdiploidy represents an important prognostic factor in childhood B‐ALL, the specific chromosome gains with prognostic value in HHD‐B‐ALL remain controversial, and...

Chronic myeloid leukaemia (CML) is a haematological neoplasm driven by the BCR/ABL fusion oncogene. The monogenic aspect of the disease and the feasibility of ex vivo therapies in haematological disorders make CML an excellent candidate for gene therapy strategies. The ability to abolish any coding sequence by CRISPR-Cas9 nucleases offers a powerfu...

Purpose To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other vascular function parameters as compared to individuals without this condition. Methods An observational study was conducted. Fifty-seven subjects di...

Objectives The Innovative Medicines Initiative–funded, multistakeholders project Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in hematologY (HARMONY) created a task force involving patient organizations, medical associations, pharmaceutical companies, and health technology assessment/regulator agencies’ representatives t...

Introduction: Conventional karyotype analysis is one of the most important diagnostic tools to determine the prognosis of acute myeloid leukemia (AML), in which more than 50% of cases are affected. However, the low sensitivity of this technique hampers the detection of small genetic alterations like Copy Number Variation (CNV) that could affect the...

The mutational status of the immunoglobuin heavy variable (IGHV) genes is an undisputable strong prognostic factor that subdivides patients with chronic lymphocytic leukemia (CLL) into 2 subgroups, i.e. IGHV-unmutated CLL (U-CLL) and IGHV-mutated CLL (M-CLL). U-CLL and M-CLL have distinct landscapes of genomic aberrations as well as distinct progno...

The large acute myeloid leukemia (AML) patient-derived data sets collected within the European HARMONY alliance allows to study the molecular heterogeneity underlying AML in detail. Especially, how cytogenetic and molecular genetic aberrations differentially affect patients. Here, we report first results on the differences in mutational patterns in...

Background: The development of new genetic profiling techniques such as Next Generation Sequencing (NGS) have helped to unravel the genomic landscape of a large number of hematological diseases. In acute myeloblastic leukemia (AML), many mutations have been found at diagnosis or during the course of the disease, either alone or in combination. Neve...

Context There is a debate regarding the impact of t(1;19) (q23;p13) in adult BCP ALL. While the MD Anderson group suggests it may be a low-risk subtype, the German, English, and French study groups have shown no differential outcome, and Italian and SWOG groups have reported poor outcomes. Objective To analyze the frequency and clinical impact of...

SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applyi...

Purpose To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other vascular function parameters as compared to individuals without this condition. Methods An observational study was conducted. Fifty-seven subjects di...

Introduction Intestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness. Met...

The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology’s complexity, bioinformatics analys...

Introduction: Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. The clinical efficacy of lenalidomide in MDS patients has been extensively reviewed and although the mechanisms of action in del(5q) clone have been previously described, in vi...

Background: Most IPSS low and int1 (lower) risk MDS patients with isolated del(5q) develop RBC TD or need treatment for symptomatic anemia early after diagnosis (median time to transfusion/treatment of 20 months, López Cadenas et al abstract 3180 ASH, 2016). Lenalidomide (LEN) is a reference treatment in MDS-del(5q) but approved in many countries o...

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph-neg adult...

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator...

Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML,...

The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis–relapse samples from 13 BCP-ALL patients to id...

The landscape of medical sequencing has rapidly changed with the evolution of next generation sequencing (NGS). These technologies have contributed to the molecular characterization of the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), through the identification of recurrent gene mutations, which are present in >80% of...

Somatic mutations in patients with myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSTC) are associated with adverse outcome, but the role of chronic graft-versus-host disease (cGVHD) in this subset of patients remains unknown. We analyzed bone marrow samples from 115 patients with MDS collected prior...

Genome-editing nucleases like the popular CRISPR/Cas9 enable the generation of knockout cell lines and null zygotes by inducing site-specific double-stranded breaks (DSBs) within a genome. In most cases, when a DNA template is not present, the DSB is repaired by nonhomologous end joining (NHEJ), resulting in small nucleotide insertions or deletions...

Introduction Hermansky-Pudlak syndrome (HPS) is an inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and, sometimes, serious clinical complications such as immunodeficiency, granulomatous colitis, and/or pulmonary fibrosis. Heterogeneous clinical symptoms and a large number of possible genetic culprits (...

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations i...

Treatment with azacitidine (AZA) has been suggested to be of benefit for higher‐risk myelodysplastic syndrome (HR‐MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR‐MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time‐varying variable i...

Small lymphocytic lymphoma (SLL) is considered as the non-leukemic form of presentation of chronic lymphocytic leukemia (CLL). We have compared the features, genomic alterations, and outcome of 890 patients with CLL and SLL. One hundred and thirteen patients presented as SLL and more frequently had unmutated-IGHV, CD38high, ZAP-70high, CD49dhigh, +...

Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in platelet production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventive treatments. Until recently, this has been performed by Sanger sequencing of a limited number of candidate genes. High-throughput se...

Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases w...

Although i(17q) [i(17q)] is frequently detected in hematological malignancies, few studies have assessed its clinical role in chronic lymphocytic leukemia (CLL). We recruited a cohort of 22 CLL patients with i(17q) and described their biological characteristics, mutational status of the genes TP53 and IGHV and genomic complexity. Furthermore, we an...

In this prospective trial, the efficacy of azacitidine in lower-risk myelodysplastic syndromes (LR-SMD) lacking del(5q) was compared to best supportive care (BSC) at 1:1. The primary endpoint was the achievement of erythroid hematologic improvement (HI-E) after nine cycles. Thirty-six patients received at least ≥1 cycle. HI-E was confirmed 44.4% ra...

The RASGRP2 gene encodes the Ca²⁺ and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), which plays a key role in integrin activation in platelets and neutrophils. We here report two new RASGRP2 variants associated with platelet dysfunction and bleeding in patients. The homozygous patients had normal platelet and neutrophil counts a...

Background: Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PS) usually produce xanthomas and premature coronary atherosclerosis, although hematological abnormalities may occasionally be present. This clinical picture is unfamiliar to many phy...

The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutation...

CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained an...

Our study aimed to analyze the presence of mutations in SF3B1 and other spliceosome-related genes in myelodysplastic syndromes with ringed sideroblasts (MDS-RS) by combining conventional Sanger and next-generation sequencing (NGS) methods, and to determine the feasibility of this approach in a clinical setting. 122 bone marrow samples from MDS-RS p...

Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are i...

Currently, molecular diagnosis of haemophilia A and B (HA and HB) highlights the excess risk-inhibitor development associated with specific mutations, and enables carrier testing of female relatives and prenatal or preimplantation genetic diagnosis. Molecular testing for HA also helps distinguish it from von Willebrand disease (VWD). Next-generatio...

The complex interplay between bone marrow-derived mesenchymal stromal cells (BM-MSC) and neoplastic hematopoietic cells is involved in the progression of myeloproliferative neoplastic (MPN) diseases. Extracellular vesicles (EV) have emerged as a complex cell-to-cell communication system within the neoplastic microenvironment. EV are able to reprogr...

DOWNLOAD at: https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-016-1290-4 --- Background: In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The sta...

Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p-) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series w...

Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative ana...

Caracterizar funcional y molecularmente 5 pacientes de 4 familias no relacionadas con diátesis hemorrágica y alteración de la agregación plaquetaria.

Advances in bioinformatics have contributed towards a significant increase in available information. Information analysis requires the use of distributed computing systems to best engage the process of data analysis. This study proposes a multiagent system that incorporates grid technology to facilitate distributed data analysis by dynamically inco...

To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) wer...

Details of chromosome 13 rearrangements in the three high-risk MDS patients affected by chromothripsis. (XLSX)

Relationship between aCGH and CC studies in the normal karyotype group. Normal karyotype patients are divided into three categories on the basis of the number of good-quality metaphases evaluated: ≤10, 11–19 and ≥20. Patients with normal and abnormal aCGH results within each category are represented by different shades of blue. (TIF)

Supplementary Methods. Additional information on patients, array-based comparative genomic hybridization studies and next-generation sequencing studies. (DOCX)

All genomic copy number changes detected by aCGH and all conventional cytogenetic information for the whole series. (XLSX)

Ensembl gene and transcript IDs for the five genes selected for NGS. (XLSX)

PCR protocols for NGS. All PCR reactions were performed in the 96-Well GeneAmp® PCR System 9700 (Applied Biosystems, Foster City, CA). (XLSX)

PCR primer-pair sequences for all amplicons representing DNMT3A (16), RUNX1 (7), TET2 (27), TP53 (8) and BCOR (29) genes. (XLSX)

PCR amplification mixes for NGS. All PCR reactions were prepared from a starting material of 30–60 ng of genomic DNA, according to the manufacturers’ recommendations. Amplification mixes #1, #2 and #4 were used with the FastStart High Fidelity PCR System, dNTPack (Roche Applied Science) and amplification mix #3 was used with the GC-RICH PCR System,...

Resumen El diagnóstico de una diátesis hemorrágica hereditaria y en particular de un trastorno plaquetario hereditario se basa en la historia clínica así como en la aplicación de las escalas de sangrado, el estudio funcional de laboratorio y en la caracterización molecular. En la actualidad se están desarrollando métodos rápidos, que requieran esca...

Objective: to analyse by FISH the frequency and prognostic impact of hyperdiploidy in CLL METHOD: A review of 1,359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution, was carried out. Hyperdiploidy was considered when a gain of at least 3 out of the 5 FISH probes used was observed RESULTS: 7 cases (0.51%) with...