Myelodysplastic syndromes (MDS) are myeloid neoplasms presenting with dysplasia in the bone marrow (BM) and peripheral cytopenia. In most patients anemia develops. We screened for genes that are expressed abnormally in erythroid progenitor cells (EP) and contribute to the pathogenesis of MDS.
View Article and Find Full Text PDFThe blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.
View Article and Find Full Text PDFFor PET imaging of mantle cell lymphoma (MCL), [F]FDG (2-deoxy-2-[F]fluoro-D-glucose) is the currently recommended radiotracer, although uptake is variable and bone marrow evaluation is limited. In this prospective study, we evaluated the novel CXCR4 (G-protein-coupled C-X-C chemokine receptor type 4) tracer [Ga]Pentixafor in MCL patients, and compared it to [F]FDG. MCL patients underwent [Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [F]FDG-PET/MRI, before treatment.
View Article and Find Full Text PDFObjective: The pancreatic uptake of [C]methionine ([C]MET) is associated with beta-cell function and insulin secretion, but [C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [C]MET in the residual pancreas following pancreaticoduodenectomy.
View Article and Find Full Text PDFThe interaction of hematopoietic stem and progenitor cells with their direct neighboring cells in the bone marrow (the so called hematopoietic niche) evolves as a key principle for understanding physiological and malignant hematopoiesis. Significant progress in this matter has recently been achieved making use of emerging high-throughput techniques that allow characterization of the bone marrow microenvironment at single cell resolution. This review aims to discuss these single cell findings in the light of other conventional niche studies that together define the current notion of the niche's implication in i) normal hematopoiesis, ii) myeloid neoplasms and iii) disease-driving pathways that can be exploited to establish novel therapeutic strategies in the future.
View Article and Find Full Text PDFBruton tyrosine kinase inhibitor ibrutinib is effective in treating chronic lymphocytic leukemia (CLL). However, after ibrutinib treatment initiation, patients frequently experience an increase of CLL blood cell count. This phenomenon in clinical practice is thought to reflect a "compartment shift" of CLL cells from lymph nodes to the peripheral blood, but the actual shifting has not yet been demonstrated.
View Article and Find Full Text PDFBackground: Patients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited.
View Article and Find Full Text PDFT-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies.
View Article and Find Full Text PDFBleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.
View Article and Find Full Text PDFPurpose: [S-methyl-C]-L-methionine ([C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [C]MET uptake.
Methods: Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.