Although the BCR/ABL tyrosine kinase inhibitor imatinib is highly effective for treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia, relapse with emerging imatinib resistance mutations in the BCR/ABL kinase domain poses a significant problem. Here, we show that the multikinase inhibitor sorafenib inhibits proliferation and induces ap...

Chronic myeloid leukemia (CML) is characterized by the presence of the constitutively active BCR-ABL protein tyrosine kinase. Using a multipotent hemopoietic cell line, FDCP-Mix, expressing BCR-ABL tyrosine kinase, we investigated the initial effects of this kinase in primitive hematopoietic stem cells. We identified down-regulation of a novel gene, CCN3, as a direct consequence of BCR-ABL kina...

The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was...

The Philadelphia chromosome was first discovered in Philadelphia in 1960. It corresponds to shortened chromosome 22 resulting from reciprocal translocation between long arm of chromosome 9 and short arm of chromosome 22, which is designated as t(9;22)(q34;q11). This gives rise to a BCR/ABL fusion gene, that juxtaposes the ABL1 gene on chromosome 9 (region q34) to a part of the BCR ("Breakpoint ...

Bcr–Abl is a chimeric oncoprotein that is strongly implicated in acute lymphoblastic (ALL) and chronic myelogenous leukemias (CML). This deregulated tyrosine kinase selectively causes hematopoietic disorders resembling human leukemias in animal models and transforms fibroblasts and hematopoietic cells in culture. Bcr–Abl also protects cells from death induced on cytokine deprivation or exposure...

the purpose of this study was to evaluate the profitability of hatchery litter recycling into poultry feedstuff supplement. the data were collected in 2011 in 4 provinces, by direct interviewing of all hatcheries which used the hatchery litter drying machine. net present value (npv), benefit-cost ratio (bcr), and internal rate of return (irr) methods were applied for this analysis. in the studi...

B lymphocytes are key players in host defence, but also autoimmune diseases. Their survival depends upon tonic signals transduced by surface immunoglobulin (BCR) and the process leading to antibody secretion is initiated by interaction of BCR with a cognate antigen. CD22 limits signalling of the BCR to strike a balance between tonic signalling, reactivity to pathogens and prevention of autoimmu...

B lymphomas account for the majority of the lymphoma cases. BCR expression appears to be important for B lymphoma because most oncogenes are translocated to nonrearranged Ig loci and because all of the variants that arise in anti-idiotypic Ab-treated lymphoma patients remain BCR positive. Based on this and the fact that BCR is required for mature B cell survival, we tested the requirement for c...