A5063314713- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Cancer, Hypoxia, and Metabolism
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Skin and Cellular Biology Research
- Biomarkers in Disease Mechanisms
- Pesticide Exposure and Toxicity
- Kruppel-like factors research
- T-cell and B-cell Immunology
- Viral-associated cancers and disorders
- Extracellular vesicles in disease
- RNA modifications and cancer
Josep Carreras Leukaemia Research Institute
2020-2025
Universitat de Barcelona
2020-2024
Instituto de Salud Carlos III
2021-2024
Leukemia Research Foundation
2021
Centro de Investigación Biomédica en Red de Cáncer
2021
Hospital del Mar Research Institute
2018
Universitat Autònoma de Barcelona
2010-2018
Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines primary blasts in vitro vivo. However, the molecular mechanisms responsible broad DOT-cell recognition of cells remain poorly understood. Here, we dissected role natural killer (NK) receptor ligands by DOT cells. Screening...
Activation of the Wnt pathway promotes progressive phosphorylation coreceptor LRP5/6 (low-density lipoprotein receptor-related proteins 5 and 6), creating a phosphorylated motif that inhibits glycogen synthase kinase 3β (GSK-3β), which in turn stabilizes β-catenin, increasing transcription β-catenin target genes. Casein 1 (CK1) family members play complex role this pathway, either as inhibitors or activators. In report, we have dissected roles CK1 isoforms early steps signaling. CK1ε is...
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
p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here required for Wnt pathway signaling. binds phosphorylated by CK1ε in response to Wnt3a. also associates the co-receptor LRP5/6, interaction mediated E-cadherin, showing unexpected physical link between adherens junctions a receptor. Depletion of abolishes binding LRP5/6 prevents activation upon Wnt3a stimulation. Elimination inhibits early responses Wnt, such as Dvl-2...
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...
Cell fate choice is a key event happening during preimplantation mouse development. From embryonic day 3.5 (E3.5) to E4.5, the inner cell mass (ICM) differentiates into epiblast (Epi, NANOG expressing cells) and primitive endoderm (PrE, GATA6, SOX17 and/or GATA4 cells). The mechanism by which ICM cells differentiate Epi PrE remains partially unknown. FGF/ERK has been proposed as main signalling pathway for this event, but it does not explain co-expression of GAT6 or how initiated. In study,...
A role for Rac1 GTPase in canonical Wnt signalling has been recently demonstrated, being required β-catenin translocation to the nucleus. In this article we have investigated mechanism of stimulation by Wnt. Up-regulation Rac1activity Wnt3a temporally correlates with enhanced p120-catenin binding and Vav2. Vav2 association is modulated phosphorylation protein: it stimulated upon serine/threonine CK1 inhibited tyrosine Src or Fyn. Acting on these two post-translational modifications, induces...
Background Although adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells (CD19-CAR T-cells) achieves high rates complete response in patients with B-cell acute lymphoblastic leukemia (B-ALL), relapse is common. Bone marrow (BM) mesenchymal stem/stromal cells (BM-MSC) are key components the hematopoietic niche and implicated B-ALL pathogenesis therapy resistance. MSC exert an immunosuppressive effect on T-cells; however, their impact CD19-CAR T-cell activity...
B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicted by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to leukemogenesis. Here, we have integrated genome-wide methylome and transcriptome data from 69 patients with de novo MLL-rearranged (MLLr) non-MLLr iB-ALL uniformly treated according Interfant-99/06 protocol. signatures...
Abstract CD19‐directed chimeric antigen receptors (CAR) T cells induce impressive rates of complete response in advanced B‐cell malignancies, specially acute lymphoblastic leukemia (B‐ALL). However, CAR T‐cell‐treated patients eventually progress due to poor T‐cell persistence and/or disease relapse. The bone marrow (BM) is the primary location for leukemia. rapid/efficient colonization BM by systemically infused CD19‐CAR might enhance activity and persistence, thus, offering clinical...
Abstract Mesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by unpredictable efficacy infusions reported multiple clinical trials. A seminal recent study showed that infused MSCs actively induced to undergo apoptosis recipient cytotoxic T cells, mechanism triggers vivo...
Canonical and noncanonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to ligands acting through canonical pathway, Wnts that activate signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation its binding Frizzled (Fz) receptor complex. The protein kinase CK 1ε is required for Dvl/Fz association both signaling. Here we show differently complex, does not require p120‐catenin with Wnt5a co‐receptor Ror2. promotes formation of Ror2–Fz complex...
Abstract Purpose: Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non–Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance phosphoproteomic profiling for early identification BTKi responders remains underexplored. Experimental Design: A set six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) TG-1701, a novel irreversible and highly specific BTKi,...
Abstract Chromosomal instability (CIN) lies at the core of cancer development leading to aneuploidy, chromosomal copy-number heterogeneity (chr-CNH) and ultimately, unfavorable clinical outcomes. Despite its ubiquity in cancer, presence CIN childhood B-cell acute lymphoblastic leukemia (cB-ALL), most frequent pediatric showing high frequencies remains unknown. Here, we elucidate aneuploid cB-ALL subtypes using single-cell whole-genome sequencing primary samples by generating functionally...
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Acute myeloid leukemia (AML) is the most common acute in adults. Patients with AML harboring a constitutively active internal tandem duplication mutation (ITDMUT) FMS-like kinase tyrosine (FLT3) receptor generally have poor prognosis. Several kinase/FLT3 inhibitors been developed and tested clinically, but very few (midostaurin gilteritinib) thus far FDA/EMA-approved for patients newly diagnosed or relapse/refractory FLT3-ITDMUT AML. Disappointingly, clinical responses are commonly partial...
ABSTRACT T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy characterized by high rates of induction failure and relapse, effective targeted immunotherapies are lacking. Despite promising clinical progress with genome-edited CD7-directed CAR-T cells, which present significant logistical regulatory issues, therapy in T-ALL remains challenging due to the shared antigen expression between malignant healthy cells. This can result fratricide, aplasia, potential for blast...
<div>AbstractPurpose:<p>Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non–Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance phosphoproteomic profiling for early identification BTKi responders remains underexplored.</p>Experimental Design:<p>A set six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) TG-1701, a novel...