The chimeric oncoprotein BCR-Abl exhibits deregulated protein tyrosine kinase activity and is responsible for the pathogenesis of certain human leukemias, such as chronic myelogenous leukemia. The activities of cellular Abl (c-Abl) and BCR-Abl are stringently regulated and the cellular mechanisms involved in their inactivation are poorly understood ...
Kotagiri Sasikumar+3 more
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Activation of tyrosinase kinase and microfilament-binding functions of c-abl by bcr sequences in bcr/abl fusion proteins. [PDF]
Chronic myelogenous leukemia and one type of acute lymphoblastic leukemia are characterized by a 9;22 chronosome translocation in which 5' sequences of the bcr gene become fused to the c-abl proto-oncogene. The resulting chimeric genes encode bcr/abl fusion proteins which have deregulated tyrosine kinase activity and appear to play an important role in
J. R. Mcwhirter, Jean Y. J. Wang
openaire +3 more sources
Activation of tyrosine kinases by mutation of the gatekeeper threonine. [PDF]
Protein kinases targeted by small-molecule inhibitors develop resistance through mutation of the gatekeeper threonine residue of the active site. Here we show that the gatekeeper mutation in the cellular forms of c-ABL, c-SRC, platelet-derived growth ...
Azam, Mohammad+4 more
core +1 more source
Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance.
Iqbal Zafar+2 more
doaj +1 more source
Mouse embryonic stem cells that express a NUP98–HOXD13 fusion protein are impaired in their ability to differentiate and can be complemented by BCR-ABL [PDF]
NUP98-HOXD13 (NHD13) fusions have been identified in patients with myelodysplastic syndrome, acute myelogenous leukemia and chronic myeloid leukemia blast crisis. We generated 'knock-in' mouse embryonic stem (ES) cells that express a NHD13 fusion gene from the endogenous murine NUP98 promoter, and used an in vitro differentiation system to ...
Slape, C.+4 more
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Targeting quiescent leukemic stem cells using second generation autophagy inhibitors [PDF]
In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs).
A Hamilton+42 more
core +2 more sources
Nanoparticle‐Mediated Targeted Protein Degradation: An Emerging Therapeutics Technology
Targeted protein degradation (TPD) has emerged as a powerful therapeutic approach, with numerous candidates molecules now advancing into clinical development. Recent innovations have incorporated nanoparticles to facilitate and enhance these degradation processes, yielding synergistic effects.
Andrew G. Baker+3 more
wiley +2 more sources
Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein [PDF]
Abstract The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leukemia (CML). Here, tandem nanospray mass spectrometry was used to demonstrate cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR on class I-negative CML cells transfected with HLA-A*0301, and on primary CML cells from HLA-A3–positive ...
Clark, RE+14 more
openaire +4 more sources
Objetive: The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia. Methods: A retrospective review was performed of
Samuel Roosevelt Campos dos Reis+8 more
doaj +1 more source
BCR ABL Fusion Protein Detection by a Modern Approach: Fluroscent Immuno Bead Assay
ABSTRACT Introduction Chronic Myeloid Leukemia (CML) is probably the most extensively studied human malignancy. CML patients (90-95%) harbor the Philadelphia (Ph) chromosome, a shortened chromosome 22, resulting from a reciprocal translocation t (9; 22) (q34; q11) between the long arms of chromosome 9 and 22, fusion ABL proto-oncogene on chromosome ...
S. Dasgupta+4 more
openaire +2 more sources