Publications associées à γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

Characterization of the gut-bone marrow axis through bile acid signaling

Communication between the intestine and other organs such as the lungs, brain or bones is mediated by several metabolites, like short-chain fatty acids or bile acids, that relay information about nutritional and microbiota status. Bile acids are endogenous ...

EPFL2024

Novel quantitative bioengineered tools to track human bone marrow niche cellular constituents in health and disease

Rita Sarkis

Acute leukemia has a high mortality rate of approximately 50%, and current methods are not effective in predicting disease progression and relapse. To improve our understanding of hematopoiesis and develop new markers for predicting disease relapse in dead ...

EPFL2023

Caspase-9-mediated cleavage of vimentin attenuates the aggressiveness of leukemic NB4 cells

Saeed Mohammadi, Cyrus Kazemiraad

Vimentin is a main type 3 intermediate filament protein. It seems that abnormal expression of vimentin is contributed to the appearance of the aggressive feature of cancer cells. So that it has been reported that malignancy and epithelial-mesenchymal trans ...

SPRINGER2023

Resistance mechanism to Notch inhibition and combination therapy in human T cell acute lymphoblastic leukemia

Linlin Cao

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy caused by acquisition of genetic alterations during T-cell development. The 5-year overall survival of pediatric T-ALL patients has improved considerably over the past 30 ...

EPFL2023

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Freddy Radtke, Ute Koch, Christelle Dubey, Nadine Fournier, Marianne Nkosi, Tara Kimberly Sugrue, Mateusz Waldemar Antoszewski, Giovanni Ciriello

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1(T315I) and BCR-ABL1(T315I-E255K)

Oliver Hantschel

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I ...

SPRINGER2021

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic le ...

EPFL2021

Notch signaling promotes disease initiation and progression in murine chronic lymphocytic leukemia

Freddy Radtke, Jessica Sordet, Ute Koch, Nadine Fournier, Marianne Nkosi, Delphine Maude Tardivon, Mateusz Waldemar Antoszewski

NOTCH1 gain-of-function mutations are recurrent in B-cell chronic lymphocytic leukemia (B-CLL), where they are associated with accelerated disease progression and refractoriness to chemotherapy. The specific role of NOTCH1 in the development and progressio ...

AMER SOC HEMATOLOGY2021

Notch Signaling - a Booster of Chronic Lymphocytic Leukemia During Initiation and Disease Progression

Delphine Maude Tardivon

Chronic lymphocytic leukemia (CLL) is a B cell malignancy and represents the most common leukemia in adults within the Western world. This disease mainly affects the elderly, with a median age of diagnosis over 70. The disease course is highly variable amo ...

EPFL2020

Characterization of myelodysplastic syndromes progressing to acute lymphoblastic leukemia

Filipe Amândio Brandão Sanches Vong Martins

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases, with a variable probability of transformation into acute leukemia, which is, in the vast majority of cases, of myeloid lineage. Nevertheless, rare cases of acute lymphoblastic leukemia ...

SPRINGER2021

Antiangiogenic immunotherapy suppresses desmoplastic and chemoresistant intestinal tumors in mice

Matthias Lütolf, Mauro Delorenzi, Laureline Wetterwald, Sina Nassiri, Michele De Palma, Mario Leonardo Squadrito, Nikolche Gjorevski, Alan Nicolas Thierry Guichard, Simone Ragusa, Borja Prat Luri

Mutations in APC promote colorectal cancer (CRC) progression through uncontrolled WNT signaling. Patients with desmoplastic CRC have a significantly worse prognosis and do not benefit from chemotherapy, but the mechanisms underlying the differential respon ...

2020

MarrowQuantAcross Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections

Nicolas Kunz, Olivier Burri, Olaia Maria Naveiras Torres-Quiroga, Vasco Ledebur de Antas de Campos, Chiheb Boussema, Frédérica Schyrr, Josefine Catharina Pedersen Tratwal, Shanti Rojas-Sutterlin, Rita Sarkis, Daniel Naveed Tavakol

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapi ...

2020

The nuclear receptor corepressor NCoR1 regulates hematopoiesis and leukemogenesis in vivo

Johan Auwerx, Wei Zhang, Lulu Liu, Na Zhang, Yao Zhang

Enhanced understanding of normal and malignant hematopoiesis pathways should facilitate the development of effective clinical treatment strategies for hematopoietic malignancies. Nuclear receptor corepressor 1 (NCoR1) has been implicated in transcriptional ...

AMER SOC HEMATOLOGY2019

Metabolic and microenvironmental strategies to accelerate hematopoietic recovery post-aplasia

Vasco Ledebur de Antas de Campos

The procedure-associated mortality rate of bone marrow transplantations (BMT) remains close to 25%. The BMT is therefore only indicated for life-threatening diseases, with no replacement of this technology to be expected in the foreseeable future. Modest i ...

EPFL2019

Cytosolic delivery and characterization of monobodies interfering with SH2 domain-phosphotyrosine interactions

Nadine Eliane Schmit

Targeted cancer therapy is a very promising concept; however, small molecule inhibitors only exist for a limited number of oncoproteins and resistance development limits their clinical use. Different engineered non-antibody scaffolds are being explored to ...

EPFL2018

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics

Romain Hamelin, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphobl ...

Nature Publishing Group2017

The Multi-kinase Inhibitor Debio 0617B Reduces Maintenance and Self-renewal of Primary Human AML CD34(+) Stem/Progenitor Cells

Michel Aguet, Maximilien Murone, Andres McAllister, Stefania Rigotti

Acute myelogenous leukemia (AML) is initiated and maintained by leukemia stem cells (LSC). LSCs are therapy-resistant, cause relapse, and represent a major obstacle for the cure of AML. Resistance to therapy is often mediated by aberrant tyrosine kinase (T ...

Amer Assoc Cancer Research2017

Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

Florence Pojer, Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Delphine Maude Tardivon, Sina Maren Reckel, Barbara Gerig, Tim Kükenshöner, Sara Raquel Pereira Pinho, Charlotte Julie Caroline Gehin

The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study ...

Springer Nature2017

Unpaired extracellular cysteine mutations of CSF3R mediate gain or loss of function

Oliver Hantschel, Tim Kükenshöner

Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g. T618I), functionally defective mutations in the extracellular domain of the granulocyte colony-stimulating factor receptor (CSF3R) have been reported only in seve ...

American Association for Cancer Research2017