A5074536109- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Erythrocyte Function and Pathophysiology
- Pluripotent Stem Cells Research
- Glioma Diagnosis and Treatment
- Mesenchymal stem cell research
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Pancreatic function and diabetes
- Telomeres, Telomerase, and Senescence
- Genetics and Neurodevelopmental Disorders
- Protein Degradation and Inhibitors
- Autophagy in Disease and Therapy
- 3D Printing in Biomedical Research
- Hemoglobinopathies and Related Disorders
- Multiple Myeloma Research and Treatments
Polish Academy of Sciences
2017-2024
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2017-2024
Abstract Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer mitochondria receptor–ligand interactions have been shown as mediators this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which identified a novel mode cross-talk—are formed in presence stroma mediate cellular vesicles to cells. Importantly,...
Colorectal cancer (CRC) is the second leading cause of death among patients in Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, response to chemotherapy, cells may undergo stress-induced premature senescence (SIPS), which typically results growth arrest. Nonetheless, these senescent were reported divide an atypical manner and thus contribute re-growth. Therefore, we examined if SIPS escape follow treatment with chemotherapeutics...
Chronic and acute myeloid leukemia evade immune system surveillance induce immunosuppression by expanding proleukemic Foxp3+ regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, relapse, shorter survival. However, mechanisms that promote in leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers effector Tregs. Using mouse model leukemia-like disease, found Rab27a-dependent secretion EVs...
The integrated stress response (ISR) facilitates cellular adaptation to unfavorable conditions by reprogramming the response. ISR activation was reported in neurological disorders and solid tumors; however, function of its role as a possible therapeutic target hematological malignancies still remain largely unexplored. Previously, we showed that is activated chronic myeloid leukemia (CML) cells correlates with blastic transformation tyrosine kinase inhibitor (TKI) resistance. Moreover,...
Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of two RNA-binding proteins, T-cell-restricted intracellular antigen (TIAR), fragile X mental retardation protein (FMRP) in regulation translation CML residing settings mimicking peripheral microenvironment (PBM) (BMM). The outcomes showed how conditions shaped process through TIAR FMRP activity, considering its relevance therapy resistance....
Natural compounds, such as resveratrol (Res), are currently used adjuvants for anticancer therapies. To evaluate the effectiveness of Res treatment ovarian cancer (OC), we screened response various OC cell lines to combined with cisplatin (CisPt) and Res. We identified A2780 cells most synergistically responding, thus optimal further analysis. Because hypoxia is hallmark solid tumor microenvironment, compared effects alone in combination CisPt (pO2 = 1%) vs. normoxia 19%). Hypoxia caused an...
Background: High heterogeneity of mesenchymal stem/stromal cells (MSCs) due to different degrees differentiation cell subpopulations poses a considerable challenge in preclinical studies. The at pluripotent-like stage represent stem population interest for many researchers worldwide, which is worthy identification, isolation, and functional characterization. In the current study, we asked whether Wharton’s jelly-derived MSCs (WJ-MSCs) express stage-specific embryonic antigen-4 (SSEA-4) can...
Intracellular transport undergoes remodeling upon cell differentiation, which involves type-specific regulators. Bone morphogenetic protein 2-inducible kinase (BMP2K) has been potentially implicated in endocytosis and differentiation but its molecular functions remained unknown. We discovered that longer (L) shorter (S) splicing variants regulate erythroid a manner unexplainable by their involvement AP-2 adaptor phosphorylation endocytosis. However, both interact with SEC16A could localize...
Abstract Mutations in isocitrate dehydrogenase 1 and 2 ( IDH1/2 ) genes occur about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation epigenetic deregulation. We assessed the prognostic significance of mutations + 398 AML normal karyotype (NK-AML), treated daunorubicine cytarabine (DA), DA cladribine (DAC), or fludarabine. IDH2 mutation was an independent favorable factor for 4-year overall survival (OS) total NK-AML population (p = 0.03, censoring at...
Pluripotent stem cells (PSCs) are characterized by the ability to self-renew as well undergo multidirectional differentiation. Culture conditions have a pivotal influence on differentiation pattern. In current study, we compared fate of mouse PSCs using two culture media: (1) chemically defined, free animal reagents, and (2) standard one relying serum supplementation. Moreover, assessed selected regulators (WNTs, SHH) PSC We showed that pattern cultured in both systems differed...
Abstract The unique bone marrow microenvironment is created by stromal cells and such physical conditions as hypoxia. Both hypoxia interactions with have a significant impact on the biology of leukemia cells, changing their sensitivity to antileukemic therapies. Thus, it crucial introduce biological systems, which enable investigation leukemia–stroma cross‐talk verification novel therapies effectiveness under niche‐mimicking conditions. Here, we established an experimental setup based...
Pluripotent stem cells convert into skeletal muscle tissue during teratoma formation or chimeric animal development. Thus, they are characterized by naive myogenic potential. Numerous attempts have been made to develop protocols enabling efficient and safe conversion of pluripotent functional in vitro. Despite significant progress the field, generation from is still challenging—i.e., currently available methods require genetic modifications, animal-derived reagents, long lasting—and,...
Abstract Intercellular communication within the bone marrow niche significantly influences leukemogenesis and sensitivity of leukemic cells to therapy. Tunneling nanotubes (TNTs) are a novel mode intercellular cross-talk. They long, thin membranous protrusions that enable direct transfer various cargo between cells. Here we show TNTs formed stromal Fluorescence confocal microscopy with 3D reconstructions, correlative light-electron electron tomography provided evidence cellular vesicles The...
Abstract Extravasation of leukemia cells implies a microenvironment change affecting the cell response to chemotherapy. Resistance is supported by adaptation extracellular conditions founded on post-transcriptional regulation gene expression. Previous studies showed that mild activation cellular stress supports therapy resistance chronic myeloid (CML) [PMID: 23095523]. To better understand CML-CP characteristics in bone marrow niche, we modeled human CML-bone (BM) crosstalk. We employed...
ABSTRACT Hypoxia rapidly alters gene expression to allow cellular adaptation challenging conditions and support tumour growth. also affects the chromatin structure by modifications of histones DNA methylation. Glioblastoma (GBM) is an aggressive, deadly primary brain for which there no effective treatment. The microenvironment GBM highly heterogeneous, with infiltration glioma-associated microglia macrophages (GAMs) presence necrotic, hypoxic regions. mechanisms through hypoxia regulates...
Abstract Integrated Stress Response (ISR) facilitates cellular adaptation to variable environmental conditions by reprogramming response. Activation of ISR was reported in neurological disorders and solid tumours, but its function hematological malignancies remains largely unknown. Previously we showed that is activated chronic myeloid leukemia (CML) CD34+ cells, activity correlates with disease progression imatinib resistance. Here demonstrate inhibition small molecule ISRIB, not PERK...
ABSTRACT Intracellular transport undergoes remodeling upon cell differentiation, which involves type-specific regulators. Bone morphogenetic protein 2-inducible kinase (BMP2K) has been potentially implicated in endocytosis and differentiation but its molecular functions remained unknown. We discovered that longer (L) shorter (S) splicing variants regulate erythroid a manner unexplainable by their involvement AP-2 adaptor phosphorylation endocytosis. However, both interacted with SEC16A whose...
Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of two RNA-binding proteins, T-cell-restricted intracellular antigen (TIAR) fragile X mental retardation protein (FMRP) in regulation translation CML residing settings mimicking peripheral microenvironment (PBM) (BMM). The outcomes showed how conditions shaped process through TIAR FMRP activity, considering its relevance therapy resistance. QuaNCAT...
Abstract Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most common primary brain tumor adults. GBM has poorest prognosis and no efficient cure to date due diffusive growth into surrounding brain, preventing complete surgical resection leading inevitable relapse. Tumor microenvironment (TME) of contains brain-residing microglia bone-marrow derived macrophages (collectively known as glioma-associated microglia/macrophages, GAMs) that constitute up 30%...
Abstract BACKGROUND Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most aggressive type of primary brain tumor. GBM has poorest prognosis with no efficient cure to date due diffusive growth into brain, resistance treatments and immunosuppressive tumor microenvironment (TME). The invasiveness supported by heterogeneous TME local microglia bone-marrow-derived macrophages (collectively known as glioma-associated macrophages, GAMs). In addition, hypoxia a...