Present studies demonstrate that treatment with arsenic trioxide (AT) lowered ectopically expressed or endogenous levels of Bcr-Abl protein, as well as induced apoptosis of Bcr-Abl-expressing cultured and primary chronic myeloid leukemia cells, including those refractory to imatinib mesylate. Treatment with AT neither affected bcr-abl mRNA transcript levels nor promoted the proteasomal degradat...

BACKGROUND The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene, which is causative for chronic myeloblastic leukemia. Because Bcr encodes a serine/threonine protein kinase, we studied its kinase activity and determined the role of Bcr in the PDGF signaling pathway to ERK1/2 activation and DNA synthesis in rat aortic smooth muscle cells (RASMCs). METHO...

Conventional cytogenetic is the standard technique for detection of Philadelphia (Ph) chromosome in chronic myeloid leukemia (CML). Evaluation of abelson murine leukemia/breakpoint cluster region (abl/bcr) fusion using dual-colour fluorescence in situ hybridization (D-FISH) is an alternative approach allowing rapid and reliable detection of the disease. We employed the technique of interphase D...

Ocular vestibular evoked myogenic potentials (oVEMPs), subjective visual vertical (SVV), and fundus photographically measured binocular cyclorotation (BCR) are diagnostic tests to assess utricular function in patients with vertigo or dizziness. In 138 chronic dizziness, we asked whether the asymmetry ratio of oVEMP (normal, right side pathological, left pathological) could predict SVV deviation...

To better understand the Philadelphia-negative (Ph-) chronic myeloid leukemia (CML) and its relationships with Philadelphia-positive (Ph+) CML and chronic myelomonocytic leukemia (CMML), a study was undertaken by the Groupe Français de Cytogénétique Hématologique. Thirty-five Ph- CML patients were investigated and compared with 55 chronic phase Ph+ CML and 100 CMML patients. There were 12 M-BCR...

The Bcr-abl oncogene induces hematopoietic cell transformation and protects cells from apoptosis; however, the mechanisms whereby Bcr-abl blocks apoptosis are poorly defined. We examined whether the inhibitor of apoptosis protein (IAP) family, in particular survivin, are regulated by Bcr-abl. Overexpression of Bcr-abl in Mo7e or BaF3 hematopoietic cells elevated survivin mRNA and protein concom...

Abstract Successful initiation of the B-cell receptor (BCR) signaling, and subsequent antigen-encounter in germinal centers are both marked by sharp increases CD25 surface-expression. Likewise, oncogenic signaling leukemia (B-ALL) lymphoma induces CD25-surface expression. While is known as an IL2-receptor chain on T- NK-cells, significance its expression B-cells was unclear. We discovered that,...

Altering the subcellular localization of signal transducing proteins is a novel approach for therapeutic intervention. Mislocalization of tumor suppressors, oncogenes, or factors involved in apoptosis results in aberrant functioning of these proteins, leading to disease. In the case of chronic myelogenous leukemia (CML), cytoplasmic Bcr-Abl causes oncogenesis/proliferation. On the other hand, n...

Bcr-Abl, a fusion protein generated by t(9;22)(q34;q11) translocation, plays a critical role in the pathogenesis of chronic myelogenous leukemia (CML). It has been shown that Bcr-Abl contains multiple functional domains and motifs and can disrupt regulation of many signaling pathways and cellular functions. However, the role of specific domains and motifs of Bcr-Abl or of specific signaling pat...

Degradation of BCR-ABL oncoproteins by heat shock protein 90 (Hsp90) inhibitors in chronic myelogenous leukemia is expected to overcome resistance to ABL tyrosine kinase inhibitors. However, the precise mechanisms still remain to be uncovered. We found that while c-Cbl E3 ligase induced ubiquitin-dependent degradation of mature and phosphorylated BCR-ABL proteins, another E3 ligase CHIP (carbox...