Person:
Hernández Sánchez, María

First Name

María

Last Name

Hernández Sánchez

URI

https://hdl.handle.net/20.500.14352/86320

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Bioquímica y Biología Molecular

Area

Bioquímica y Biología Molecular

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 11

From Biomarkers to Models in the Changing Landscape of Chronic Lymphocytic Leukemia: Evolve or Become Extinct
(Cancers, 2021) González Gascón y Marín, Isabel; Muñoz Novas, Carolina; Rodríguez Vicente, Ana-Eugenia; Quijada Álamo, Miguel; Hernández Sánchez, María; Pérez Carretero, Claudia; Ramos Ascanio, Victoria; Hernández Rivas, José Ángel
hronic lymphocytic leukemia (CLL) is an extremely heterogeneous disease. With the advent of oral targeted agents (Tas) the treatment of CLL has undergone a revolution, which has been accompanied by an improvement in patient’s survival and quality of life. This paradigm shift also affects the value of prognostic and predictive biomarkers and prognostic models, most of them inherited from the chemoimmunotherapy era but with a different behavior with Tas. This review discusses: (i) the role of the most relevant prognostic and predictive biomarkers in the setting of Tas; and (ii) the validity of classic and new scoring systems in the context of Tas. In addition, a critical point of view about predictive biomarkers with special emphasis on 11q deletion, novel resistance mutations, TP53 abnormalities, IGHV mutational status, complex karyotype and NOTCH1 mutations is stated. We also go over prognostic models in early stage CLL such as IPS-E. Finally, we provide an overview of the applicability of the CLL-IPI for patients treated with Tas, as well as the emergence of new models, generated with data from patients treated with Tas.
Cine en compañía para prevenir enfermedades
(2023) Valderrama Conde, María José; Linares Gómez, María; Ayllón Santiago, Tania; De Francisco Martínez, Patricia; Bravo Vázquez, Daniel Antonio; López Ejeda, Noemí; Marrodán Serrano, María Dolores; Juan Chocano, María Del Carmen De; García Redondo, Alberto; Hernández Sánchez, María; López Vázquez de la Torre, Mª de la O ; Alonso Monge, Rebeca María Del Mar; Díez Orejas, Rosalía María; Navarro González De Mesa, Elisa; Ancos Pintado, Raquel ; Campo Moreno, Rosa del ; Rodríguez García, Alba ; García Vicente, Roberto ; Álvarez Sánchez-Redondo, Noemí ; Hernando Ospina, Natalia ; Rodríguez Solana, Patricia ; Pulido Vadillo, Mario ; León Rodríguez, Sergio ; Álvaro Llorente, Laura ; Pedrero Tomé, Roberto ; Alaminos Torres, Ana
El proyecto atiende la necesidad social de colectivos desfavorecidos o en riesgo de exclusión (sin hogar, presidiarios, discapacitados o enfermos mentales, mujeres) de ayuda al conocimiento sobre determinadas enfermedades que les afectan con una incidencia más alta que al resto de población (infecciosas, metabólicas, mentales, derivadas de consumo de drogas o alcohol o malnutrición). Adicionalmente, acusan carencias de compañía, entretenimiento o posibilidad de socialización, derivadas de sus circunstancias vitales. Los estudiantes que cursan titulaciones del ámbito de ciencias y ciencias de la salud profundizan en el aprendizaje de estas enfermedades realizando un servicio a estas personas de acompañamiento e información sobre prevención y/o tratamiento de las mismas. Trabajan en equipos multidisciplinares (distintas titulaciones y cursos) y desarrollan competencias profesionales en salud pública, así como transversales, como colaboración y coordinación en equipo, análisis crítico, expresión oral o diseño de materiales. Las actividades de servicio se llevan a cabo mediante visitas a los centros sociales asociados, donde se acompaña a los colectivos con proyección de películas sobre las enfermedades de interés, realización de juegos y coloquio. El proyecto comenzó en el curso 2017-18 (dentro de la convocatoria INNOVA) y ha ampliado el ámbito de conocimiento (bioquímica, biología molecular, epidemiología, microbiología, nutrición), facultades/organismos (Facultades de Biología, Farmacia, Medicina, Químicas, Hospitales 12 de Octubre y Ramón y Cajal), departamentos (Bioquímica y Biología molecular, Genética, Fisiología y Microbiología, Microbiología y Parasitología, Biodiversidad, Ecología y Evolución), asignaturas / titulaciones de los estudiantes, tipo de enfermedades abordadas y grupos y centros sociales atendido (distintas entidades y Ayuntamiento de Madrid).
Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications
(International Journal of Cancer, 2020) Pérez‐Carretero, Claudia; Hernández Sánchez, María; González, Teresa; Quijada‐Álamo, Miguel; Martín‐Izquierdo, Marta; Vidal, María‐Jesús; García de Coca, Alfonso; Hernández Rivas, José Ángel; Aguilar, Carlos; Vargas‐Pabón, Manuel; Alonso, Sara; Sierra, Magdalena; Rubio‐Martínez, Araceli; Dávila, Julio; Díaz‐Valdés, José R.; Queizán, José‐Antonio; Benito, Rocío; Rodríguez‐Vicente, Ana E.; Hernández‐Rivas, Jesús‐María
Chromosome 14q32 rearrangements/translocations involving the immunoglobulinheavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). Theprognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement(IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profilewith recurrent mutations in BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genesrelated to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treat-ment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q−, normal fluorescence in situ hybridization (FISH) and +12 CLL, NOTCH1, SF3B1, TP53, BIRC3 and BRAF werealso mutated. The presence of these mutations not only was an independent risk fac-tor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients(13q−/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status ofIGHby FISH analysis to refine the risk-stratification CLL model.
CRISPR/Cas9 in Chronic Lymphocytic Leukemia
(Encyclopedia, 2022) Hernández Sánchez, María
Genome-editing systems such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology have uncovered new opportunities to model diseases such as chronic lymphocytic leukemia. CRISPR/Cas9 is an important means of advancing functional studies of Chronic Lymphocytic Leukemia (CLL) through the incorporation, elimination and modification of somatic mutations in CLL models.
A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia
(Plos One, 2015) Hernández Rivas, José Ángel; Hernández Sánchez, María; Rodríguez-Vicente, Ana Eugenia; Grossmann, Vera; Collado, Rosa; Heras, Cecilia ; Puiggros, Anna; Martín, Ana África; Puig, Noemí; Benito, Rocío; Robledo, Cristina; Delgado, Julio; González, Teresa; Queizán, José Antonio; Galende, Josefina; Fuente, Ignacio de la; Martín-Núñez, Guillermo; Alonso, José María; Abrisqueta, Pau; Luño, Elisa; Marugán, Isabel; González-Gascón, Isabel; Bosch, Francesc; Kohlmann, Alexander; González, Marcos; Espinet, Blanca; Hernández-Rivas, Jesús María; Spencer B. Gibson
To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) (P<0.0001). In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008). The absence of splenomegaly (P = 0.02), low LDH (P = 0.018) or β2M (P = 0.006), and the presence of 11q-L (P = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50% vs 94.1%, P = 0.023). In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes.
Loss-of-function lesions impact B-cell development and fitness but are insufficient to drive CLL in mouse models
(2023) Hacken, Elisa ten; Yin, Shanye; Redd, Robert; Hernández Sánchez, María; Clement, Kendell; Brunsting Hoffmann, Gabriela; Regis,Fara F.; Witten, Elizabeth; Li, Shuqiang; Neuberg, Donna; Pinello, Luca; Livak, Kenneth J.; Wu, Catherine J.
Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14
(Plos One, 2012) Rodríguez, Ana Eugenia; Hernández, Jose Ángel; Benito, Rocío; Gutiérrez, Norma ; García, Juan Luis; Hernández Sánchez, María; Risueño, Alberto; Sarasquete, M. Eugenia; Fermiñán, Encarna; Fisac, Rosa; García de Coca, Alfonso; Martín-Núñez, Guillermo; Heras, Natalia de las; Recio, Isabel; Gutiérrez, Oliver; Rivas, Javier De Las; González, Marcos; Hernández-Rivas, Jesús
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 with a high number of 13q- cells (13q-H) had both shorter overall survival and time to first therapy. The goal of the study was to analyze the genetic profile of 13q-H patients. Design and Methods: A total of 102 samples were studied, 32 of which served as a validation cohort and five were healthy donors. Results Chronic lymphocytic leukemia patients with higher percentages of 13q- cells (>80%) showed a different level of gene expression as compared to patients with lower percentages (<80%, 13q-L). This deregulation affected genes involved in apoptosis and proliferation (BCR and NFkB signaling), leading to increased proliferation and decreased apoptosis in 13q-H patients. Deregulation of several microRNAs, such as miR-15a, miR-155, miR-29a and miR-223, was also observed in these patients. In addition, our study also suggests that the gene expression pattern of 13q-H cases could be similar to the patients with 11q- or 17p-. Conclusions This study provides new evidence regarding the heterogeneity of 13q deletion in chronic lymphocytic leukemia patients, showing that apoptosis, proliferation as well as miRNA regulation are involved in cases with higher percentages of 13q- cells.
High-Throughput CRISPR Screening in Hematological Neoplasms
(Cancers, 2022) Ancos-Pintado, Raquel; Bragado-García, Irene; Morales, María Luz; García-Vicente, Roberto; Arroyo-Barea, Andrés; Rodríguez-García, Alba; Martínez López, Joaquín; Linares Gómez, María; Hernández Sánchez, María
CRISPR is becoming an indispensable tool in biological research, revolutionizing diverse fields of medical research and biotechnology. In the last few years, several CRISPR-based genome-targeting tools have been translated for the study of hematological neoplasms. However, there is a lack of reviews focused on the wide uses of this technology in hematology. Therefore, in this review, we summarize the main CRISPR-based approaches of high throughput screenings applied to this field. Here we explain several libraries and algorithms for analysis of CRISPR screens used in hematology, accompanied by the most relevant databases. Moreover, we focus on (1) the identification of novel modulator genes of drug resistance and efficacy, which could anticipate relapses in patients and (2) new therapeutic targets and synthetic lethal interactions. We also discuss the approaches to uncover novel biomarkers of malignant transformations and immune evasion mechanisms. We explain the current literature in the most common lymphoid and myeloid neoplasms using this tool. Then, we conclude with future directions, highlighting the importance of further gene candidate validation and the integration and harmonization of the data from CRISPR screening approaches.
The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab
(British Journal of Haematology, 2016) Forero‐Castro, Maribel; Robledo, Cristina; Lumbreras, Eva; Benito, Rocio; Hernández‐Sánchez, Jesús M.; Hernández Sánchez, María; García, Juan L.; Corchete‐Sánchez, Luis A.; Tormo, Mar; Barba, Pere; Menárguez, Javier; Ribera, Jordi; Grande, Carlos; Escoda, Lourdes; Olivier, Carmen; Carrillo, Estrella; García de Coca, Alfonso; Ribera, Josep‐María; Hernández‐Rivas, Jesús M.
The introduction of Rituximab has improved the outcome and survivalrates of Burkitt lymphoma (BL). However, early relapse and refractorinessare current limitations of BL treatment and new biological factors affectingthe outcome of these patients have not been explored. This study aimed toidentify the presence of genomic changes that could predict the response tonew therapies in BL. Forty adolescent and adult BL patients treated withthe Dose-Intensive Chemotherapy Including Rituximab (Burkimab) proto-col (Spanish Programme for the Study and Treatment of HaematologicalMalignancies; PETHEMA) were analysed using array-based comparativegenomic hybridization (CGH). In addition, the presence ofTP53, TCF3(E2A), ID3andGNA13mutations was assessed by next-generationsequencing (NGS). Ninety-seven per cent of the patients harboured geno-mic imbalances. Losses on 11q, 13q, 15q or 17p were associated with apoor response to Burkimab therapy (P=0 038), shorter progression-freesurvival (PFS;P=0 007) and overall survival (OS;P=0 009). The integra-tive analysis of array-CGH and NGS showed that 26 3% (5/19) and 36 8%(7/19) of patients carried alterations in theTP53andTCF3genes, respec-tively.TP53alterations were associated with shorter PFS (P=0 011) whileTCF3alterations were associated with shorter OS (P=0 032). Geneticstudies could be used for risk stratification of BL patients treated with theBurkimab protocol.
Next-generation sequencing and FISH studies reveal the appearance of gene mutations and chromosomal abnormalities in hematopoietic progenitors in chronic lymphocytic leukemia
(Journal of Hematology and Oncology, 2017) Quijada-Álamo, Miguel; Hernández Sánchez, María; Robledo, Cristina; Hernández-Sánchez, Jesús-María; Benito, Rocío; Montaño, Adrián; Rodríguez-Vicente, Ana E; Quwaider, Dalia; Martín, Ana-África; García-Álvarez, María; Vidal-Manceñido, María Jesús; Ferrer-Garrido, Gonzalo; Delgado-Beltrán, María-Pilar; Galende, Josefina; Rodríguez, Juan-Nicolás; Martín-Núñez, Guillermo; Alonso, José-María; García de Coca, Alfonso; Queizán, José A.; Sierra, Magdalena; Aguilar, Carlos; Kohlmann, Alexander; Hernández,José-Ángel; González, Marcos; Hernández-Rivas, Jesús-María
Background Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as a mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, the presence of both chromosomal aberrations and gene mutations in CD34+ cells from the same patients has not been explored. Methods Amplicon-based deep next-generation sequencing (NGS) studies were carried out in magnetically activated-cell-sorting separated CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1 genes. In addition, ultra-deep NGS was performed in a subset of seven patients to determine the presence of mutations in flow-sorted CD34+CD19− early hematopoietic progenitors. Fluorescence in situ hybridization (FISH) studies were performed in the CD34+ cells from nine patients of the cohort to examine the presence of cytogenetic abnormalities. Results NGS studies revealed a total of 28 mutations in 24 CLL patients. Interestingly, 15 of them also showed the same mutations in their corresponding whole population of CD34+ progenitors. The majority of NOTCH1 (7/9) and XPO1 (4/4) mutations presented a similar mutational burden in both cell fractions; by contrast, mutations of TP53 (2/2), FBXW7 (2/2), and SF3B1 (3/4) showed lower mutational allele frequencies, or even none, in the CD34+ cells compared with the CD19+ population. Ultra-deep NGS confirmed the presence of FBXW7, MYD88, NOTCH1, and XPO1 mutations in the subpopulation of CD34+CD19− early hematopoietic progenitors (6/7). Furthermore, FISH studies showed the presence of 11q and 13q deletions (2/2 and 3/5, respectively) in CD34+ progenitors but the absence of IGH cytogenetic alterations (0/2) in the CD34+ cells. Combining all the results from NGS and FISH, a model of the appearance and expansion of genetic alterations in CLL was derived, suggesting that most of the genetic events appear on the hematopoietic progenitors, although these mutations could induce the beginning of tumoral cell expansion at different stage of B cell differentiation. Conclusions Our study showed the presence of both gene mutations and chromosomal abnormalities in early hematopoietic progenitor cells from CLL patients.