A5073158132- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Genomic variations and chromosomal abnormalities
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Neuroblastoma Research and Treatments
- Signaling Pathways in Disease
- Multiple Myeloma Research and Treatments
- Genomics and Rare Diseases
- Cytomegalovirus and herpesvirus research
- Mosquito-borne diseases and control
- Eosinophilic Disorders and Syndromes
- Acute Lymphoblastic Leukemia research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
Instituto de Investigación Sanitaria La Fe
2019-2025
Lund University
2018-2019
Abstract Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL ) rearrangements ( -R). These often subclonal and their biological impact remains unclear. Using a retroviral myeloid mouse model, we demonstrate that FLT3 ITD , N676K NRAS G12D accelerate - MLLT3 onset. Further, also disease, possibly by providing stimulatory factors. Herein, show one such factor, MIF, promotes survival of initiating cells. We identify acquired de novo Braf Cbl Kras Ptpn11...
Article16 July 2019Open Access Source DataTransparent process Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma Sofie Mohlin Corresponding Author [email protected] orcid.org/0000-0002-2458-3963 Division Pediatrics, Department Clinical Sciences, Lund University, Lund, Sweden Search for more papers by this author Karin Hansson Laboratory Medicine, Translational Cancer Research, University Center, Katarzyna Radke Sonia Martinez orcid.org/0000-0003-2230-7794...
Rare diseases (RDs) often have a genetic basis, yet conventional diagnostic techniques fail to identify causative variations in up 50% of cases. Structural variants (SVs), including balanced rearrangements, frequently evade detection by karyotyping, microarray, and exome sequencing. The present study utilized optical genome mapping (OGM) investigate two patients with RDs whose etiology remained unresolved despite prior genomic analyses. Patient 1 exhibited reciprocal translocation disrupting...
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype unavailable a significant proportion of patients. Optical genome mapping (OGM) promising technique that allows high-resolution chromosomal aberrations (structural variants, copy number loss heterozygosity) single workflow. In this study, peripheral blood samples from series 21 patients were analyzed via OGM. We assessed the clinical impact application OGM...
Abstract RNA splicing and epigenetic gene mutations are the most frequent genetic lesions found in patients with myelodysplastic neoplasm (MDS). About 25% of present concomitant such pathways, suggesting a cooperative role MDS pathogenesis. Importantly, factor ZRSR2 frequently associate alterations regulator TET2 . However, impact these concurrent hematopoiesis remains unclear. Using CRISPR/Cas9 genetically engineered mice, we demonstrate that Zrsr2 m/m Tet2 −/− promote reduced penetrance....
Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic molecular alterations. Despite the increased knowledge prognostic importance genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice a validated manner, conventional karyotype remains mandatory evaluation suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation...
Mutations in splicing factors are recurrent somatic alterations identified myelodysplastic syndromes (MDS) and they frequently coincide with mutations epigenetic factors. About 25% of patients present concurrent such pathways, suggesting a cooperative role the pathogenesis MDS. We focused on factor U2AF1 involved recognition 3′ splice site during pre-mRNA splicing. Using CRISPR/Cas9 system, we created heterozygous mice carboxy-terminal truncated U2af1 allele (U2af1mut/+), studied U2af1mut/+...
Cytogenomic analyses of hematological malignancies require the use different techniques, whether combined or on isolation, for detection chromosomal abnormalities.Optical genomic mapping (OGM) is a new technology based analysis long DNA molecules fluorescently labelled in specific sequences that create unique pattern, allowing simultaneous numerical and structural abnormalities with higher sensitivity (up to 5%) precision than karyotyping.The aim this review describe methodological...
Topic: 23. Hematopoiesis, stem cells and microenvironment Background: The gold standard technique for cytogenetics diagnosis is chromosome banding analysis (CBA). However, there a limitation of the procedures. CBA requires metaphases alteration needs minimum size 5 Mpb to be detected. Optical Genome Mapping (OGM) novel high-throughput diagnostic method that may overcome drawbacks cytogenetic approaches. OGM can detect structural variants (SVs), copy number variations (CNV), balanced or...
Background: Mutations in splicing factors and epigenetic regulators are the most frequent genetic alterations patients with myelodysplastic syndromes (MDS). The minor spliceosome factor ZRSR2 regulator TET2 appear significantly associated MDS patients. However, functional impact of such mutations hematopoietic system have been scarcely studied. To address this question, we established a murine model (Zrsr2m/mTet2−/−) carrying both genes, which exhibited signs compatible disease mice....