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Concept

Leucémie

Publications associées (31)

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

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, Nadine Fournier, Mateusz Waldemar Antoszewski, Marianne Nkosi, Tara Kimberly Sugrue, Christelle Dubey

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

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

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

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

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

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

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

Malva pseudolavatera Leaf Extract Promotes ROS Induction Leading to Apoptosis in Acute Myeloid Leukemia Cells In Vitro

Rita Sarkis

Malva pseudolavatera Webb & Berthel. is a plant from the Malvaceae family that has long been included in the human diet due to its various curative effects. Many plant leaf extracts from the various species of Malva genus have been reported to possess anti ...

MDPI2020

In Vivo Pre-Instructed HSCs Robustly Execute Asymmetric Cell Divisions In Vitro

Matthias Lütolf, Mukul Girotra, Aline Roch, Vincent Trachsel

Hematopoietic stem cells (HSCs) are responsible for life-long production of all mature blood cells. Under homeostasis, HSCs in their native bone marrow niches are believed to undergo asymmetric cell divisions (ACDs), with one daughter cell maintaining HSC ...

2020

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

Oliver Hantschel, Jörg Hülsken, Anja Irmisch

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ ...

2019

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

Michel Aguet

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

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

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

Romain Hamelin, Sandrine Madeleine Suzanne Georgeon, Oliver Hantschel, 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

T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNF alpha Expression and Empower Adoptive Cell Therapy for Solid Tumors

Melody Swartz

Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reprod ...

Amer Assoc Cancer Research2017

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

Targeting macrophages sensitizes chronic lymphocytic leukemia to apoptosis and inhibits disease progression

Michele De Palma

The role of monocytes/macrophages in the development and progression of chronic lymphocytic leukemia (CLL) is poorly understood. Transcriptomic analyses show that monocytes/macrophages and leukemic cells cross talk during CLL progression. Macrophage deplet ...

Elsevier2016

Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases

Oliver Hantschel

Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examine ...

American Society of Hematology2016

Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis

Oliver Hantschel, Sina Maren Reckel

The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. Effective implementation of personalized medicine will require t ...

American Association for Cancer Research2016