A5074537201- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Multiple Myeloma Research and Treatments
- Immunodeficiency and Autoimmune Disorders
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Blood disorders and treatments
- Histone Deacetylase Inhibitors Research
- Telomeres, Telomerase, and Senescence
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Cancer therapeutics and mechanisms
- Acute Lymphoblastic Leukemia research
- Lymphoma Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Erythrocyte Function and Pathophysiology
- Parvovirus B19 Infection Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Hematological disorders and diagnostics
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
The University of Texas MD Anderson Cancer Center
2015-2024
Clinica Universidad de Navarra
2024
Centro de Investigación Biomédica en Red de Cáncer
2024
Gunma University
2019
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2015
Universidad de Alcalá
2010-2014
Cleveland Clinic
2013
Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and associated with high remission rates prolonged survival intensive chemotherapy. NPM1 rare myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), the clinical outcomes of these patients, when treated chemotherapy, unknown. We retrospectively evaluated clinicopathologic characteristics impact therapy 31 patients MDS MDS/MPN mutations. Next-generation sequencing was performed at diagnosis...
Abstract Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due lack approved second-line treatment options. As cancer the seeds disease progression, we investigated biological properties HSCs that drive evolution, seeking uncover...
The prognostic and predictive value of sequencing analysis in myelodysplastic syndromes (MDS) has not been fully integrated into clinical practice. We performed whole exome (WES) bone marrow samples from 83 patients with MDS 31 MDS/MPN identifying 218 driver mutations genes 98 (86%) patients. A total 65 (57%) received therapy hypomethylating agents. By univariate analysis, BCOR, STAG2, TP53 SF3B1 significantly influenced survival. Increased number (≥ 3), but clonal heterogeneity, predicted...
RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk resistance to and progression after hypomethylating agent (HMA) therapy, the current standard care for disease. Here, using single-cell, multi-omics technologies, we seek dissect biological mechanisms underlying initiation pathway-mutated CMML. We identify that mutations induce transcriptional reprogramming hematopoietic stem progenitor cells (HSPCs)...
Abstract PAX4 is a key regulator of pancreatic islet development whilst in adult acute overexpression protects β-cells against stress-induced apoptosis and stimulates proliferation. Nonetheless, sustained expression promotes β-cell dedifferentiation hyperglycemia, mimicking failure diabetic patients. Herein, we study mechanisms that allow stringent regulation endowing favorable adaptation response to changing environment without loss identity. To this end, was monitored using mouse bearing...
Myelodysplastic syndromes (MDS) are characterized by impaired proliferation and differentiation of hematopoietic stem cells. The participation toll-like receptor (TLR)-mediated signaling in MDS is well documented. Increased TLR leads to the constitutive activation NF-κB, which mediates inflammation, cell apoptosis. In addition, pathway induces expression miRNAs participate fine-tuning inflammatory response. also regulate other biological processes, including hematopoiesis. miR-125a miR-125b...
Abstract KDM6B is an epigenetic regulator that mediates transcriptional activation during differentiation, including in bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). Overexpression of has been reported BM HSPCs patients with myelodysplastic syndromes (MDS) chronic myelomonocytic leukemia (CMML). Whether the overexpression contributes to pathogenesis these diseases remains be elucidated. To study this, we generated a Vav-KDM6B mouse model, which overexpresses compartment....
Abstract Purpose: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated outcomes this combination HR-MDS incompletely understood. Experimental Design: We pooled patient data from 3 prospective trials evaluating HMA–venetoclax in to study associations between overall response rate (ORR), survival (OS), event-free (EFS). Kaplan–Meier method was used estimate...
Abstract The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape mouse human cells attrition, as induced by pathogenic germline variants telomerase complex genes. Here, show attrition maintains persistent metabolic activation differentiation towards megakaryocytic lineage through...
Abstract The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the by which myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain be elucidated. Here, we show expansion MDS hematopoietic stem cells (HSCs) a granulo-monocytic-biased transcriptional differentiation state who initially responded eventually relapsed. While HSCs undifferentiated cellular are sensitive...
Abstract SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks a specific MDS subtype, ringed sideroblasts (MDS-RS), is characterized by accumulation erythroid precursors bone marrow and primarily affects elderly population. Here, using single-cell technologies functional validation studies primary SF3B1-mutant MDS-RS samples, we show that mutations lead to activation EIF2AK1 pathway response heme deficiency targeting this rescues aberrant...
Abstract DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome damage, we investigate how become resistant antisense oligonucleotide (ASO) targeting Interleukin enhancer binding factor 2 (ILF2), regulator that overexpressed 70% of patients whose disease has progressed after standard therapies have failed. Here, show undergo adaptive metabolic rewiring restore energy balance and promote...
Mutations in CSF3R have been recently defined as the common genetic event patients with myeloid neoplasms, including rare entity known chronic neutrophilic leukemia (CNL),1, 2, 3 becoming a potentially useful biomarker for diagnosing and therapy target.4 encodes transmembrane receptor granulocyte colony-stimulating factor (G-CSF; CSF3), which provides proliferative survival signal granulocytes also contributes to their differentiation function.5 Although there are several studies on massive...
LILRB4 is expressed in AML M4/M5 cells and negatively regulates immune cell activation via T-cell suppression. Its expression role chronic myelomonocytic leukemia (CMML) myelodysplastic syndrome (MDS) are unknown. We investigated 19 CMML 27 MDS patients correlated it with response to subsequent hypomethylating agent (HMA) therapy. RNA was increased when compared healthy controls (q < 0.1) slightly who responded HMAs > 0.1). Pathway analysis revealed upregulation of PD-1 signaling, CTLA-4...