Leucémie myéloïde chronique

Science de la nature
Biologie
Biologie cellulaire
Cycle cellulaire

Publications associées (27)

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

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

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

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

Michel Aguet, Stefania Rigotti, Maximilien Murone, Andres McAllister

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

CRISPR-Cas9-mediated saturated mutagenesis screen predicts clinical drug resistance with improved accuracy

Jeffrey David Jensen, Sebastian Matuszewski

Developing tools to accurately predict the clinical prevalence of drug-resistant mutations is a key step toward generating more effective therapeutics. Here we describe a high-throughput CRISPR-Cas9-based saturated mutagenesis approach to generate comprehe ...

National Academy of Sciences2017

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

Allosteric regulation and targeting of Abl SH2-kinase interface and other cytoplasmic tyrosine kinases

Allan Joaquim Lamontanara

Due to their central role in normal cellular physiology, the activity of protein kinases is tightly regulated and their aberrant activation can lead to cancer. Chronic myelogenous leukemia (CML) is a blood cancer characterized by unregulated growth of myel ...

EPFL2016

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

Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface

Oliver Hantschel, Allan Joaquim Lamontanara, Barbara Gerig

Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase do ...

American Society for Biochemistry and Molecular Biology2016

Functional Perturbation of the Gab2 Multiprotein Complex by High-affinity SH2-binding Monobodies in Chronic Myelogenous Leukemia

Emel Basak Gencer Akçok

Chronic myeloid leukemia is characterized by a reciprocal chromosomal translocation between chromosome 9 and 22, resulting in the expression of the Bcr-Abl oncoprotein. Despite the great improvement in patient survival using tyrosine kinase inhibitors (TKI ...

EPFL2015

Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2 domain on kinase activity

Oliver Hantschel

Constitutive activation of the non-receptor tyrosine kinase c-Abl (cellular Abelson tyrosine protein kinase 1, Abl1) in the Bcr (breakpoint cluster region)-Abl1 fusion oncoprotein is the molecular cause of chronic myeloid leukaemia (CML). Recent studies ha ...

Portland Press2015

Targeting BCR-ABL and JAK2 in Ph+ ALL

Oliver Hantschel

In this issue of Blood, Appelmann et al provide evidence for prolonged survival and prevention of resistance in a mouse model of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) by combined targeting of the BCR-ABL kinase and Janus ...

2015

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