Interferon-alpha (IFN-alpha) induces cytogenetic responses of variable degree in patients with chronic myelogenous leukemia (CML). We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive 2-step reverse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-alpha. A total of 250 peripheral blood and 55 b...

Chronic myeloid leukemia (CML) is characterized by the presence of a 210-kD protein (P210bcr-abl) in the cytoplasm of leukemic cells, generated by the reciprocal translocation between chromosome 9 and chromosome 22. Due to this translocation, the abl oncogene is coupled to the bcr gene, forming a new determinant in this protein encoded by the bcr-abl joining region. In the joining region itself...

4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]benzamide methanesulfonate (STI571) is the first successful target-based drug with excellent potency against chronic myelogenous leukemia. Studies on this compound have illuminated potentials and problems of kinase inhibitors in the treatment of cancer. As found in crystal structures, STI571-bound Abe...

Nonreceptor tyrosine kinase Abl is an actin-binding protein and a key regulator of neuronal axonal development. Although Abl family kinases also are localized in dendrites and are implicated in postsynaptic functions, it is not clear how Abl kinases regulate dendritic morphogenesis. Using a developing hippocampal culture as a model, we found that the inhibition of Abl kinases by STI571 leads to...

Acquired pointmutationswithin the BCR-ABL kinase domain represent a commonmechanismof resistance to ABL inhibitor therapy in patients with chronic myeloid leukemia (CML). The BCR-ABL mutant is highly resistant to imatinib, nilotinib, and dasatinib, and is frequently detected in relapsed patients. This critical gap in resistance coverage drove development of DCC-2036, an ABL inhibitor that binds...

The is study examined the relationships between the microbial composition of the subgingival plaque, contact loss caused by caries and alveolar bone loss (ABL) in primary molars. The study included 10 children with contact loss in at least two sites, one with ABL and one without ABL, and 10 children without ABL with sites with or without contact loss. The microbial composition of subgingival pl...

Limited information is available regarding AmpC β-lactamase (ABL)-producing Enterobacteriaceae compared to extended-spectrum β-lactamase-producing enterobacteria. Since ABL-producing organisms are often resistant to multiple antimicrobial agents, therapeutic options against these pathogens are limited. Among 230 clinical Enterobacteriaceae isolates, 64 (27.8%) were found to produce ABL in our s...

Many extracellular and intracellular signals promote the c-Abl tyrosine kinase activity. c-Abl in turn triggers a multitude of changes either in protein phosphorylation or in gene expression in the cell. Yet, c-Abl takes part in diverse signaling routes because of several domains linked to its catalytic core. Complex conformational changes turn on and off its kinase activity. These changes affe...

This chapter will briefly describe the Alignment-Based Learning (ABL) framework and relate it to Data-Oriented Parsing from different viewpoints. Firstly, ABL can be used to bootstrap an initial treebank, which can then be used by DOP. Secondly, ABL can be used to enhance the robustness of DOP. Thirdly, a DOP model can be used to disambiguate ambiguous syntactic structures found during the lear...

We present a high-resolution (2.0 A) crystal structure of the catalytic domain of a mutant form of the Abl tyrosine kinase (H396P; Abl-1a numbering) that is resistant to the Abl inhibitor imatinib. The structure is determined in complex with the small-molecule inhibitor VX-680 (Vertex Pharmaceuticals, Cambridge, MA), which blocks the activity of various imatinib-resistant mutant forms of Abl, i...