A5035133175- Hematopoietic Stem Cell Transplantation
- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Platelet Disorders and Treatments
- Erythrocyte Function and Pathophysiology
- Neonatal Respiratory Health Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CRISPR and Genetic Engineering
Karolinska Institutet
2021-2024
Karolinska University Hospital
2023
Abstract Rare multipotent stem cells replenish millions of blood per second through a time-consuming process, passing multiple stages increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight need for more rapid replenishment from cells, established models hematopoiesis implicate only one mandatory differentiation pathway each cell lineage. Here, we establish nonhierarchical relationship between distinct that all lineages and almost exclusively...
Abstract Acute myeloid leukemia (AML), the most frequent in adults, is driven by recurrent somatically acquired genetic lesions a restricted number of genes. Treatment with tyrosine kinase inhibitors has demonstrated that targeting prevalent FMS-related receptor 3 (FLT3) gain-of-function mutations can provide significant survival benefits for patients, although efficacy FLT3 eliminating FLT3-mutated clones variable. We identified T cell (TCR) reactive to D835Y driver mutation domain (TCR...
Abstract Unlike chimeric antigen receptors, T-cell receptors (TCRs) can recognize intracellular targets presented on human leukocyte (HLA) molecules. Here we demonstrate that T cells expressing TCRs specific for peptides from the lymphoid-specific enzyme terminal deoxynucleotidyl transferase (TdT), in context of HLA-A*02:01, specifically eliminate primary acute lymphoblastic leukemia (ALL) T- and B-cell origin vitro three mouse models disseminated B-ALL. By contrast, treatment spares normal...
Abstract Relapse after complete remission (CR) remains the main cause of mortality allogeneic stem cell transplantation for hematological malignancies and, therefore, improved biomarkers early prediction relapse a critical goal toward development and assessment preemptive treatment. Because significance cancer cells as source relapses unclear, we investigated whether mutational screening persistence rare would enhance measurable residual disease (MRD) transplantation. In retrospective study...