A5016773523- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Single-cell and spatial transcriptomics
- Acute Lymphoblastic Leukemia research
- Erythrocyte Function and Pathophysiology
- Blood disorders and treatments
- Parvovirus B19 Infection Studies
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Hematopoietic Stem Cell Transplantation
- RNA modifications and cancer
- Renal Diseases and Glomerulopathies
- Retinoids in leukemia and cellular processes
- Advanced Chemical Sensor Technologies
- Insect Pheromone Research and Control
- Monoclonal and Polyclonal Antibodies Research
- Multiple Myeloma Research and Treatments
- Viral-associated cancers and disorders
- Neutropenia and Cancer Infections
- Health, Environment, Cognitive Aging
Josep Carreras Leukaemia Research Institute
2015-2024
Universitat Autònoma de Barcelona
2016-2024
Institut Català d'Oncologia
2017-2024
Vall d'Hebron Hospital Universitari
2024
Vall d'Hebron Institute of Oncology
2024
Vall d'Hebron Institut de Recerca
2024
Fundación Josep Carreras Contra la Leucemia
2016-2022
Universitat de Barcelona
2015-2019
Abstract Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy myeloid malignancies. Hypomethylating agents (HMA), azacitidine, have become standard-of-care to treat myelodysplastic syndromes (MDS), neoplasms can evolve into acute leukemia. However, our capacity identify who will respond HMAs, and the duration response, remains limited. To shed light on this question, we leveraged unprecedented analytic power...
The indexed individual, from now on termed M116, was the world's oldest verified living person January 17th 2023 until her passing August 19th 2024, reaching age of 117 years and 168 days (https://www.supercentenarian.com/records.html). She a Caucasian woman born March 4th 1907 in San Francisco, USA, Spanish parents settled Spain since she 8. Although centenarians are becoming more common demographics human populations, so-called supercentenarians (over 110 old) still rarity. In Catalonia,...
Abstract While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34 + progenitors from MDS patients, we have identified cells harboring deletion, characterizing transcriptional impact of this genetic insult disease pathogenesis and treatment response. Interestingly, both non-del(5q) present similar lesions, indicating that all cells, not...
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...
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which only one defined by cytogenetic abnormality that makes these patients candidates to be treated lenalidomide. During last decade, single cell (SC) analysis has emerged as powerful tool decipher clonal architecture and further understand cancer other diseases at higher resolution level compared bulk...
<p>Clonal landscape of MDS patients</p>
<p>Impact of AZA treatment on mutant cell populations in patients with hematological improvement (HI)</p>
<div>Abstract<p>Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy myeloid malignancies. Hypomethylating agents (HMA), azacitidine, have become standard-of-care to treat myelodysplastic syndromes (MDS), neoplasms can evolve into acute leukemia. However, our capacity identify who will respond HMAs, and the duration response, remains limited. To shed light on this question, we leveraged...
<p>Karyotype and mutations (bulk NGS single-cell DNAseq) at diagnosis for the studied MDS cases</p>
<p>Clonal evolution of responder and nonresponder patients with MDS upon AZA treatment. <b>A,</b> Clonal phylogenies #3 #14 (responders) #4 #8 (nonresponders) at diagnosis. Dot size represents clone size. <b>B,</b> Fishplots (nonresponders), illustrating the clonal distribution diagnosis after <b>C,</b> Proportion mutant cells (left) predominant (right) in Dx, diagnosis; Aza, treatment.</p>
<p>Distribution of mutant cells within the BM compartments defined by immunophenotype. <b>A,</b> Percentage progenitor, immature erythroid and myeloid (Pro_Ery_Mye) compared with lymphoid in each patient at diagnosis (top); percentage (bottom, left); or T, B, NK right) diagnosis. <b>B,</b> UMAP from all samples colored number mutations per cell (left); type proportions according to (right). <b>C,</b> gene mutational status. WT, wild-type; MUT,...
<p>Effect of AZA treatment on wild-type cell populations in responder patients</p>
<p>Distribution of mutations in CHIP-associated genes at diagnosis according to response status</p>
<p>Karyotype and mutations (bulk NGS single-cell DNAseq) at diagnosis for the studied MDS cases</p>
<p>Antibodies used for single cell surface protein sequencing</p>
<p>Amplicon coverage for the custom single cell DNA sequencing panel</p>