A5011249206- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Protein Degradation and Inhibitors
- Viral-associated cancers and disorders
- Hemoglobinopathies and Related Disorders
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Histiocytic Disorders and Treatments
- Bone and Joint Diseases
- Genomic variations and chromosomal abnormalities
- Sarcoma Diagnosis and Treatment
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Retinoids in leukemia and cellular processes
- Eosinophilic Disorders and Syndromes
- Otitis Media and Relapsing Polychondritis
- Autoimmune and Inflammatory Disorders Research
- Vascular Tumors and Angiosarcomas
- Immune Cell Function and Interaction
Karolinska University Hospital
2015-2025
Karolinska Institutet
2015-2025
Integrated Cardio Metabolic Centre
2021
Canada's Michael Smith Genome Sciences Centre
2021
Queen's University Belfast
2013
Royal Bournemouth Hospital
2013
Fred Hutch Cancer Center
2013
Dana-Farber Cancer Institute
2013
Cancer Research Center
2013
Heidelberg University
2013
BACKGROUND: Risk stratification and therapeutic decision-making for myelodysplastic syndromes (MDS) are based on the International Prognostic Scoring System–Revised (IPSS-R), which considers hematologic parameters cytogenetic abnormalities. Somatic gene mutations not yet used in risk of patients with MDS. METHODS: To develop a clinical-molecular prognostic model (IPSS-Molecular [IPSS-M]), pretreatment diagnostic or peridiagnostic samples from 2957 MDS were profiled 152 genes. Clinical...
To determine the frequency of TP53 mutations and level p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) to assess their impact on disease progression.Pre- postprogression bone marrow (BM) samples from 55 consecutive patients International Prognostic Scoring System low risk (n = 32) or intermediate-1 23) were studied next-generation sequencing TP53. IHC for was performed 148 sequential BM samples.TP53 a median clone size 11% (range,...
To assess the effect of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) treatment on survival and leukemic transformation in myelodysplastic syndrome (MDS).We compared long-term outcome patients with MDS treated EPO G-CSF (n = 121) untreated 237) using multivariate Cox regression delayed entry, for first time adjusting all major prognostic variables (WHO classification, karyotype, cytopenias, level transfusion-need, age, sex).The erythroid response rate to was 39%,...
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that more common in patients aged ≥ 60 years and incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC versus nontransplantation therapies older MDS stratified by International Prognostic Scoring System (IPSS)
Abstract Cancer is a genetic disease, but two patients rarely have identical genotypes. Similarly, differ in their clinicopathological parameters, how genotypic and phenotypic heterogeneity are interconnected not well understood. Here we build statistical models to disentangle the effect of 12 recurrently mutated genes 4 cytogenetic alterations on gene expression, diagnostic clinical variables outcome 124 with myelodysplastic syndromes. Overall, one or more lesions correlate expression...
Myelodysplastic syndromes (MDSs) are a group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral blood cytopenias. Lenalidomide has dramatic therapeutic effects in patients with low-risk MDS chromosome 5q31 deletion, resulting complete cytogenetic remission >60% patients. The molecular basis this remarkable drug response is unknown. To gain insight into the targets lenalidomide we investigated its vitro on growth, maturation, global gene...
The transcriptome of the CD34+ cells was determined in a group 10 patients with 5q- syndrome using comprehensive array platform, and compared from 16 healthy control subjects 14 refractory anaemia normal karyotype. majority genes assigned to commonly deleted region (CDR) at 5q31-q32 showed reduction expression levels syndrome, consistent loss one allele. Candidate showing haploinsufficiency included tumour suppressor gene SPARC RPS14, component 40S ribosomal subunit. Two mapping CDR, RBM22...
As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a transcriptome-based assay stratification acute leukemia (AML). Comparison ribonucleic acid sequencing (RNA-Seq) to whole genome exome reveals standalone RNA-Seq offers the greatest diagnostic return, enabling identification expressed gene fusions, single nucleotide short...
PURPOSE Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced risk. METHODS Patients MDS planned HSCT were enrolled in a prospective, observational study evaluating association between MRD clinical outcome. We collected bone marrow (BM) peripheral blood samples until relapse, death, or end 24...
Abstract Background The GOSSAMER phase 2 study assessed the FMS ‐like tyrosine kinase 3 (FLT3) inhibitor gilteritinib as maintenance therapy in patients with FLT3 –internal tandem duplication ( ‐ITD) acute myeloid leukemia (AML) first complete remission without previous hematopoietic stem cell transplantation (HSCT). Methods Patients had to be within months of their last consolidation cycle and have completed recommended number cycles per local practice. inhibitors were allowed only during...
Refractory Anemia with Ring Sideroblasts (RARS) is an acquired myelodysplastic syndrome (MDS) characterized by excess iron accumulation in the mitochondria of erythroblasts. The pathogenesis RARS and cause this unusual pattern deposition remain unknown. We considered that inherited X-linked sideroblastic anemia ataxia (XLSA/A) might be informative for disorder, RARS. XLSA/A caused partial inactivating mutations ABCB7 ATP-binding cassette transporter gene, which functions to enable transport...
Clonal heterogeneity has not been described in patients with myelodysplastic syndrome isolated del(5q), for which lenalidomide emerged as a highly potent treatment. However, transformation to acute myeloid leukemia is occasionally observed, particularly without cytogenetic response lenalidomide. We performed molecular studies patient classical 5q- complete erythroid and partial lenalidomide, who evolved high-risk complex karyotype. Immunohistochemistry of pre-treatment marrow biopsies...
In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect age sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data FLT3-ITD NPM1 dating to 2007, 1570 adult patients younger than 75 years, excluding promyelocytic leukemia, had results reported. Females more often FLT3ITD and/or NPM1mut (FLT3ITD: female,...
Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates lacking. In this study, we characterized, defined the over time studied prognostic implications all t-AML patients diagnosed Sweden between 1997 2015. Data were retrieved from nationwide population-based registries. total, 6,779 included whom 686 (10%) had t-AML. The median age for was 71 years 392 (57%) females. During study period, almost doubled with a yearly increase 4.5% (95%...
Abstract We evaluated malignancy-associated hemophagocytic lymphohistiocytosis (mal-HLH) in Sweden regarding population-based incidence, clinical features, and survival. From 1997 to 2018, we identified 307 adults (≥18 years old) 9 children (209 males, 107 females; P < .001) with both an HLH-related diagnosis malignant disease, corresponding 0.19 per 100 000 annually (0.15/100 for the entire population), increasing from 0.026 (1997-2007) 0.34 (2008-2018) (P .001). In latest 7-year...
Summary We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14 , which is required for maturation 40S subunits and maps to commonly deleted region, in 5q− syndrome. Patients with Diamond‐Blackfan anaemia (DBA) show closely related protein RPS19, a consequent downregulation multiple ribosomal‐ translation‐related genes. By analogy DBA, we investigated expression profiles large group genes CD34 + cells 15 myelodysplastic syndrome (MDS) patients syndrome, 18 MDS...