A5061459080- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Virus-based gene therapy research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes and associated disorders
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Neuroblastoma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- RNA and protein synthesis mechanisms
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- Insect Resistance and Genetics
Universitat de Barcelona
2018-2025
Josep Carreras Leukaemia Research Institute
2018-2024
Instituto de Salud Carlos III
2021-2024
Spanish Clinical Research Network
2024
Leukemia Research Foundation
2021
Institute for Biomedicine
2020
Linköping University
2019
Lund University
2014-2018
Instituto de Biología Funcional y Genómica
2012-2015
Universidad de Salamanca
2012-2015
The tight control of wild-type p53 by mainly MDM2 in normal cells is permanently lost tumors harboring mutant p53, which exhibit dramatic constitutive hyperstabilization that far exceeds tumors. Importantly, critical for oncogenic gain function vivo. Current insight into the mechanism this dysregulation fragmentary and largely derived from ectopically constructed cell systems. knock-in mice established tissues have sufficient enzymatic reserves other E3 ligases to maintain full p53. We find...
Abstract Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape highly purified human bone HSCs displaying varying degrees dormancy. We identify orphan receptor GPRC5C,...
Background Acute myeloid leukemia (AML) is a hematopoietic malignancy which biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies refractory or relapse (R/R) are challenging because absence universal pan-AML target shared expression antigens normal stem/progenitor cells (HSPCs), may lead to life-threating on-target/off-tumor...
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant stem cells (LSCs) that reside specific bone marrow niches. Hypoxia signaling maintains quiescent metabolically relaxed state, desensitizing them to chemotherapy. This suggests hypothesis hypoxia contributes chemoresistance AML-LSCs may represent therapeutic target sensitize Here, we identify HIF
Conditional knockout mice are commonly used to study the function of specific genes in hematopoiesis. Different promoters that drive Cre expression have been utilized, with interferon-inducible Mx1-Cre still being most "deleter strain" experimental hematology. However, different pitfalls associated this system could lead misinterpretation functional studies. We present here two these issues related use Mx1-Cre: first, a high spontaneous recombination rate when applying techniques hematology,...
CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR persistence or resistance of either CD19+ CD19- B-ALL clones. CD22 is a pan-B marker whose expression maintained both and relapses. CD22-CAR been clinically used patients, although also occurs. engineered with tandem (Tan-CAR) containing single construct CD19 scFvs may be...
Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging disease with dismal prognosis. Despite the revolutionary impact of CD19-directed chimeric antigen receptor (CAR19)-T cell therapy, >50% patients relapse within year. Both cell-intrinsic factors favoring immune escape and poor CAR-T persistence contribute significantly to clinical failure. Moreover, expression checkpoint receptors (ICRs) their ligands complex bone marrow (BM) microenvironment...
Leukemia stem cells (LSCs) share numerous features with healthy hematopoietic (HSCs). G-protein coupled receptor family C group 5 member (GPRC5C) is a regulator of HSC dormancy. However, GPRC5C functionality in acute myeloid leukemia (AML) yet to be determined. Within patient AML cohorts, high levels correlated poorer survival. Ectopic Gprc5c expression increased aggression through the activation NF-κB, which resulted an altered metabolic state intracellular branched-chain amino acids...
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...
Loss of p53 function is a common feature human cancers and it required for differentiated tumor cell maintenance; however, not known whether sustained inactivation the pathway needed cancer stem persistence. Chronic myeloid leukemia (CML) caused by chromosome translocation that generates BCRABL oncogene encoding constitutively active protein tyrosine kinase. The disease originates in hematopoietic maintained leukemic cells (LSCs). Treatment with specific kinase inhibitors does eliminate LSCs...
Acute myeloid leukemia (AML) is the most common acute in adults. Disease heterogeneity well documented, and patient stratification determines treatment decisions. Patient-derived xenografts (PDXs) from risk-stratified AML are crucial for studying biology testing novel therapeutics. Despite recent advances PDX modeling of AML, reproducible engraftment human primarily limited to high-risk (HR) cases, with inconsistent or very protracted observed favorable-risk (FR) intermediate-risk (IR)...
Relapse of acute myeloid leukemia (AML) remains a significant clinical challenge due to limited therapeutic options and poor prognosis. Leukemic stem cells (LSCs) are the cellular units responsible for relapse in AML, strategies that target LSCs thus critical. One proposed potential strategy this end is break quiescent state LSCs, thereby sensitizing conventional cytostatics. The hypoxia-inducible factor (HIF) pathway main driver quiescence target, with precedence from both solid cancers...