The Philadelphia chromosome (Ph1), observed in greater than 90% of chronic myelogenous leukemia (CML) patients, results from a specific chromosomal translocation involving the c-abl gene. The translocation breakpoint occurs near c-abl and correlates with the production of an altered c-abl mRNA. In the CML-derived cell line K562, Ph1 is accompanied by a structurally altered c-abl protein (P210c-...

More than 95% of patients with chronic myelogenous leukemia (CML) contain an abnormal chromosome termed the Philadelphia chromosome (Ph1). Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. The product of the fused BCR-ABL genes is a protein of about 2000 amino acids termed P210 BCR-ABL. Although the BCR-ABL protein can be routinely detected in blood cells from bla...

Phagocytosis of Ab-coated pathogens is mediated through FcγRs, which activate intracellular signaling pathways to drive actin cytoskeletal rearrangements. Abl and Arg define a family of nonreceptor tyrosine kinases that regulate actin-dependent processes in a variety of cell types, including those important in the adaptive immune response. Using pharmacological inhibition as well as dominant ne...

Although the BCR-ABL hybrid gene on chromosome 22q-plays a pivotal role in the pathogenesis of chronic myeloid leukemia (CML), little is known of the reciprocal chimeric gene, ABL-BCR, formed on chromosome 9q+. By reverse transcription/polymerase chain reaction amplification (RT/PCR) we have detected ABL-BCR mRNA in cells from 31 of 44 BCR-ABL positive CML patients and 3 of 5 CML cell lines. Of...

The COOH-terminal domain of the NR2D subunit of the NMDA receptor contains proline-rich regions that show striking homology to sequences known to bind to Src homology 3 (SH3) domains. To determine whether the proline-rich region of the NR2D subunit interacts with specific SH3 domains, in vitro SH3 domain binding assays were performed. A proline-rich fragment of the NR2D subunit (2D(866-1064)) b...

A chromosomal translocation uniquely associated with chronic myeloid leukemia leads to the formation of a chimeric gene, bcr-abl, on the Philadelphia chromosome. The BRC-ABL protein displays an uncontrolled tyrosine kinase activity similar to that seen with the transforming oncogene of the Abelson murine leukemia (ABL) virus (v-abl). An interleukin 3 dependent cell line, IC.DP, has been transfe...

It has been suggested that the BCR-ABL gene of chronic myeloid leukemia (CML) is not uniformly expressed in Philadelphia (Ph)-positive cells, and that BCR-ABL gene expression precludes transcription of the normal BCR or ABL genes. Therefore, we have analyzed granulocyte-macrophage colony-forming unit (CFU-GM) colonies derived from peripheral blood of 11 CML patients by cytogenetic and by revers...

A chromosomal translocation uniquely associated with chronic myeloid leukemia leads to the formation of a chimeric gene, bcr-abl, on the Phil adelphia chromosome. The BRC-ABL protein displays an uncontrolled tyrosine kinase activity similar to that seen with the transforming onco gene of the Abelson murine leukemia (ABL) virus (\-abl). An interleukin 3 dependent cell line, IC.DP, has been trans...

The P210bcr/abl protein is associated with virtually every case of human chronic myelogenous leukemia. Unlike the related P160gag/v-abl oncogene product of Abelson murine leukemia virus, P210bcr/abl does not transform NIH 3T3 fibroblasts. To assess whether P210bcr/abl might transform hematopoietic cell types, retroviral constructs encoding P210bcr/abl were used to infect the bone marrow-derived...

Oligomerization of the nonreceptor tyrosine kinase c-Abl can activate its transforming potential. Domains mediating oligomerization within the BCR-ABL and TEL-ABL oncoproteins are required for transforming activity, and fusion of inducible dimerization domains to c-Abl can generate chimeric proteins with dimerization-dependent transforming activity. We have found that c-Abl oligomerizes at high...