María Hernández‐Sánchez
A5050004865- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Calcium signaling and nucleotide metabolism
- CAR-T cell therapy research
- Advanced Breast Cancer Therapies
- Acute Lymphoblastic Leukemia research
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Galectins and Cancer Biology
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Renal Diseases and Glomerulopathies
- Retinal Diseases and Treatments
- Single-cell and spatial transcriptomics
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Retinal Imaging and Analysis
- Glaucoma and retinal disorders
- PARP inhibition in cancer therapy
- Monoclonal and Polyclonal Antibodies Research
- Hemoglobinopathies and Related Disorders
- Pancreatic function and diabetes
Universidad Complutense de Madrid
2022-2025
Instituto de Investigación Biomédica de Salamanca
2015-2025
Universidad de Salamanca
2015-2025
Centro de Investigación del Cáncer
2015-2025
Research Institute Hospital 12 de Octubre
2024
Hospital de Galdakao
2024
Complejo Hospitalario de Salamanca
2018-2022
Dana-Farber Cancer Institute
2018-2021
Broad Institute
2018-2021
Ministerio de Ciencia, Innovación y Universidades
2020
Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on immunoglobulin heavy variable (IGHV) somatic hypermutation (SHM) status. In this study, we assessed nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) pre-treatment samples from 4580 CLL, using time-to-first-treatment (TTFT) as primary end-point relation to IGHV SHM Mutations were detected 1588 (34.7%)...
// Anna Puiggros 1, 2 , Rosa Collado 3 Maria José Calasanz 4 Margarita Ortega 5 Neus Ruiz-Xivillé 6 Alfredo Rivas-Delgado 7 Elisa Luño 8 Teresa González 9 Blanca Navarro 10 MaDolores García-Malo 11 Alberto Valiente 12 Ángel Hernández 13 María Ardanaz 14 Ángeles Piñan 15 Laura Blanco 16 Hernández-Sánchez 17 Ana Batlle-López 18 Rocío Salgado 19 Marta Salido Ferrer Pau Abrisqueta Eva Gimeno 1...
Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, presence of both chromosomal aberrations and gene mutations cells from same patients not explored. Amplicon-based deep next-generation sequencing (NGS) were carried out magnetically activated-cell-sorting separated CD19+...
In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still importance. We determined frequency and prognostic impact somatic mutations in children adult cases B-ALL treated Spanish PETHEMA SEHOP protocols.Mutational status hotspot regions TP53, JAK2, PAX5, LEF1, CRLF2 IL7R genes was by next-generation deep sequencing 340 patients (211 129 adults). The associations between mutation clinicopathological...
Background Patients with chronic lymphocytic leukemia and 13q deletion as their only FISH abnormality could have a different outcome depending on the number of cells displaying this aberration. Thus, cases high 13q- (13q-H) had both shorter overall survival time to first therapy. The goal study was analyze genetic profile 13q-H patients. Design Methods: A total 102 samples were studied, 32 which served validation cohort five healthy donors. Results Chronic patients higher percentages (>80%)...
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 constitutive of BCR-ABL p210. Using this approach, pools Boff-p210-edited cells and single edited cell-derived clones were obtained functionally studied vitro. The loss resulted ability grow absence IL-3, as Baf/3 parental showing significantly increased apoptosis levels. Notably, clone carrying...
Abstract CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables analysis Cas9-introduced edits thousands single cells. Using this technology, we analyze Ba/F3 cells engineered express or multiplexed loss-of-function recurrent chronic lymphocytic leukemia. Our approach reliably quantifies mutational co-occurrences, zygosity status, and occurrence Cas9 at single-cell resolution.
Abstract The deletion of 11q (del(11q)) invariably comprises ATM gene in chronic lymphocytic leukemia (CLL). Concomitant mutations this the remaining allele have been identified 1/3 CLL cases harboring del(11q), being biallelic loss associated with adverse prognosis. Although introduction targeted BCR inhibition has significantly favored outcomes del(11q) patients, responses patients functional through inactivation are unexplored, and development resistances to therapies increasingly...
Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing recurrent CLL loss-of-function drivers mice and recapitulated process transformation from indolent into large cell lymphoma [i.e., Richter syndrome (RS)]. Evolutionary trajectories 64 carrying diverse combinatorial gene...
Chronic lymphocytic leukemia (CLL) is a clinically and genetically heterogenous disease. Recent next-generation sequencing (NGS) studies have uncovered numerous low-frequency mutated genes in CLL patients, with SAMHD1 emerging as candidate driver gene. However, the biological clinical implications of mutations remain unclear. Using CRISPR/Cas9, we generated models to investigate impact deficiency on pathogenesis explore therapeutic strategies. Moreover, performed NGS treatment-naïve patients...
Abstract Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), prognostic significance somatic ATM mutations remains uncertain. We evaluated effects aberrations (del(11q) and/or mutations) on time-to-first-treatment (TTFT) 3631 untreated patients with CLL, context IGHV gene mutational status and nine CLL-related genes. were present 246 cases (6.8%), frequently co-occurring (112/246 cases, 45.5%). -mutated displayed a different spectrum genetic...
The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting cell cycle arrest interruption of ribosomal activity, critical factors aging cancer. In this study, we identified described the pivotal role RNA-binding protein (RBP) HNRNPK ribosome dynamics. We developed vitro model endogenous overexpression vivo mouse ubiquitous overexpression. These models showed disruptions translation caused...
Abstract Purpose We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response ranibizumab in neovascular age‐related macular degeneration (AMD). Methods A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three‐injection loading phase, pro re nata regimen was followed. Nine SNP s from six different genes ( CFH , CFB ARMS 2, SERPINF 1, VEGFR VEGF ) genotyped. Non‐genetic...
Abstract The prognosis of chronic lymphocytic leukemia (CLL) patients displaying trisomy 12 (+12) remains unclear. In this study, we analyzed the influence proportion cells with +12, and other clinical biologic factors, in time to first therapy (TTFT) overall survival (OS), 289 diagnosed CLL carrying +12. Median OS was 129 months. One hundred seventy‐four (60.2%) presented +12 <60% cells. TTFT for subgroup were longer than ≥60% cells, a median 49 months (CI95%, 39–58) vs 30 22–38) ( P =...
Abstract Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy chain ( IGH ) are rarely detected in chronic lymphocytic leukemia (CLL). The prognostic significance of translocation is controversial and its mutational profile remains unknown. Here, we present for first time a comprehensive next‐generation sequencing (NGS) analysis 46 CLL patients with rearrangement (IGH R ‐CLLs) demonstrate that ‐CLLs have distinct recurrent mutations NOTCH1 , IGLL5 POT1 BCL2 FBXW7...
We have learnt in the last decades that majority of galaxies belong to high density regions interconnected a sponge-like fashion. This large-scale structure is characterised by clusters, filaments, and walls, where most concentrate, but also under-dense called voids. The void within represent an ideal place for study galaxy formation evolution, as they are largely unaffected complex physical processes transform high-density environments. may hold key answer current challenges Lambda CDM...
To analyze the impact of 11q deleted (11q-) cells in CLL patients on time to first therapy (TFT) and overall survival (OS), 2,493 with were studied. 242 (9.7%) had 11q-. Fluorescence situ hybridization (FISH) studies showed a threshold 40% be optimal for showing that clinical differences terms TFT OS within 11q- CLLs. In ≥40% losses (11q-H) (74%), median was 19 months compared 44 <40% del(11q) (11q-L) (P<0.0001). multivariate analysis, only presence 11q-L, mutated IGHV status, early Binet...
Summary The introduction of Rituximab has improved the outcome and survival rates Burkitt lymphoma ( BL ). However, early relapse refractoriness are current limitations treatment new biological factors affecting these patients have not been explored. This study aimed to identify presence genomic changes that could predict response therapies in . Forty adolescent adult treated with Dose‐Intensive Chemotherapy Including (Burkimab) protocol (Spanish Programme for Study Treatment Haematological...
The presence of SF3B1 gene mutations is a hallmark refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize Myelodysplastic Syndrome (MDS-RS) are not completely understood. In order to gain insight in molecular basis MDS-RS, an integrative study expression and mutational status genes related mitochondrial metabolism was carried out. A total 231 low-risk MDS patients 81 controls were studied. Gene analysis revealed function...