A5002653694- Acute Myeloid Leukemia Research
- Sarcoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Medical Imaging and Pathology Studies
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- Hematopoietic Stem Cell Transplantation
- Bone Tumor Diagnosis and Treatments
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Virus-based gene therapy research
- Eosinophilic Disorders and Syndromes
- Advanced biosensing and bioanalysis techniques
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
Lund University
2016-2025
Brigham and Women's Hospital
2011-2017
Harvard University
2011-2016
Skåne University Hospital
2010
Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9 and 22 giving rise to constitutively active tyrosine kinase P210 BCR/ABL1. Therapeutic strategies aiming for cure of CML will require full eradication Ph chromosome-positive (Ph + ) stem cells. Here we used gene-expression profiling identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CD34 cells also cord blood...
Significance Acute myeloid leukemia (AML) is a hematologic malignancy with poor survival. Current treatment chemotherapy does not target the leukemic cells specifically and associated severe side effects. Here we demonstrate that antibodies directed at cell surface molecule IL-1 receptor accessory protein (IL1RAP), expressed on immature AML cells, show strong antileukemic effects in mice transplanted human mechanism behind killing through recruitment of effector cells. Using against IL1RAP...
Chronic myeloid leukemia (CML) is currently treated with tyrosine kinase inhibitors, but these do not effectively eliminate the CML stem cells. As a consequence, cells persist and cause relapse in most patients upon drug discontinuation. Furthermore, no effective therapy exists for advanced stages of disease. Interleukin-1 receptor accessory protein (IL1RAP; IL1R3) coreceptor interleukin-1 type 1 has been found upregulated on Here, we show that primitive (CD34+CD38-) cells, contrast to...
Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor new therapies are needed. We found that casein kinase 1 α (Csnk1a1), a serine-threonine kinase, is essential for AML cell in vivo. Normal hematopoietic stem progenitor cells (HSPCs) were relatively less affected by shRNA-mediated knockdown Csnk1a1. To identify downstream mediators Csnk1a1 critical cells, we performed an vivo pooled shRNA screen gene expression...
Purpose: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid (LGFMS). Some tumors display morphologic characteristics of both SEF and LGFMS, hence they are known as hybrid SEF/LGFMS. Despite the overlap gene fusion variants between these two tumor types, much more aggressive. The current study aimed further characterize SEF/LGFMS genetically better understand role characteristic genes possible additional genetic...
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients cured. The major drawbacks regarding TKIs their low efficacy in eradicating leukemic stem cells responsible disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing flow-sorted primitive (CD34+CD38low) progenitor (CD34+ CD38+) phase CML cells, identified transcriptional upregulation 32 cell surface molecules relative to...
Acute myeloid leukemia (AML) is initiated and propagated by stem cells (LSCs), a self-renewing population of responsible for therapy resistance. Hence, there an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed in vivo CRISPR knockout screen potential targets interrogating cell surface dependencies The facilitated glucose transporter type 1 (GLUT1) emerged as critical metabolic dependency LSCs murine MLL::AF9-driven model AML. GLUT1 disruption genetic...
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...
Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth survival cytokine screen using fluorescently labeled cells. RNA-sequencing revealed an IL4-induced upregulation Stat6 target genes enrichment apoptosis-related gene expression signatures. Consistent with these findings, we found IL4 stimulation induced phosphorylation disruption...
Acute myeloid leukemia (AML) is defined by an accumulation of immature blasts in the bone marrow. To identify key dependencies AML stem cells vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes syngeneic MLL-AF9 mouse model and show that CXCR4 top regulator growth survival. Deletion Cxcr4 eradicates vivo without impairing their homing to In contrast, ligand CXCL12 dispensable for development recipient mice. Moreover, expression mutated variants reveals signaling essential...
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Dysregulation of cytokines in the bone marrow (BM) microenvironment promotes acute myeloid leukemia (AML) cell growth. Due to complexity and low throughput vivo stem-cell based assays, studying role BM niche a screening setting is challenging. Here, we developed an ex cytokine screen using 11 arrayed molecular barcodes, allowing for competitive readout leukemia-initiating capacity. With this approach, assessed effect 114 murine on MLL-AF9 AML mouse cells identified tumor necrosis factor...