Bcr-Abl plays a critical role in the pathogenesis of chronic myelogenous leukemia (CML). It was previously shown that expression of Bcr-Abl in bone marrow cells by retroviral transduction efficiently induces a myeloproliferative disorder (MPD) in mice resembling human CML. This in vivo experimental system allows the direct determination of the effect of specific domains of Bcr-Abl, or specific ...

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1...

In the majority of Philadelphia (Phi-positive chronic myeloid leukemia (CML) patients, the c-ab/ gene is fused to the bcr gene, resulting in the transcription of an 8.5 kb chimeric bcr-ab/ mRNA. which is translated into a fusion protein. In about 50% of the Ph-positive acute lymphoid leukemias (ALL), the bcr-ab1 gene fusion is identical to CML, while in 50% an alternative fusion between these t...

Inhibitors of B-cell receptor (BCR) and pre-BCR signaling were successfully introduced into patient care for various subtypes of mature B-cell lymphoma (e.g., ibrutinib, idelalisib). Acute lymphoblastic leukemia (ALL) typically originates from pre-B cells that critically depend on survival signals emanating from a functional pre-BCR. However, whether patients with ALL benefit from treatment wit...

هدفت البحث الى بناء مقياس الدافعية على عينة من اللاعبين الشباب بالكرة الطائرة بأعمار (17-19) سنة، واستخدم الباحثان المنهج الوصفي بالأسلوب المسحي، وتم اختيار مجتمع بالطريقة العمدية وهم أعمار 17-19 وبعد استخراج القدرة التميزية والاتساق الداخلي والتحليل العاملي، تبين ان فقرات يلائم العينة وان لديهم مستوى عالٍ الدافعية، التوصل والذي تم بناءه لأول مرة قبل اللاعبين، ويوصي بوجوب استخدام هذا المقياس وتط...

The differentiation and apoptosis-sensitizing effects of the Bcr-Abl-specific tyrosine kinase inhibitor CGP57148B, also known as STI-571, were determined in human Bcr-Abl-positive HL-60/Bcr-Abl and K562 cells. First, the results demonstrate that the ectopic expression of the p185 Bcr-Abl fusion protein induced hemoglobin in the acute myeloid leukemia (AML) HL-60 cells. Exposure to low-dose cyto...

PURPOSE B-cell receptor (BCR)-mediated signaling is important in the pathogenesis of a subset of diffuse large B-cell lymphomas (DLBCL) and the BCR-associated kinases SYK and BTK have recently emerged as potential therapeutic targets. We sought to identify a signature of activated BCR signaling in DLBCL to aid the identification of tumors that may be most likely to respond to BCR-pathway inhibi...

BACKGROUND The bcr-abl fusion gene is the pathological origin of chronic myeloid leukemia (CML) and plays a critical role in the resistance of imatinib. Thus, bcr-abl disruption-based novel therapeutic strategy may warrant exploration. In our study, we were surprised to find that the characteristics of bcr-abl sequences met the design requirements of zinc finger nucleases (ZFNs). METHODS We c...

Both clinical and experimental evidence illustrate that p190 and p210 BCR/ABL oncogenic tyrosine kinases induce resistance to DNA damage and confer an intrinsic genetic instability. Here, we investigated whether BCR/ABL expression could modulate nucleotide excision repair (NER). We found that ectopic expression of p210 BCR/ABL in murine lymphoid BaF3 cell line inhibited NER activity in vitro, p...