The chimeric BCR/ABL protein is characteristic of Philadelphia (Ph)' leukemia because it is the direct product of the Ph translocation and it has been shown to play a causal role in the genesis of leukemia. The BCR/ABL protein exhibm a deregulated tyrosine-kinase activity capable of phosphorylating different cellular substrates in vivo and in vitro. CRKL, an adaptor protein consisting of SH2 an...

Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcription factors linking extracellular signals to target gene transcription. Hematopoietic cells express two highly conserved STAT5-isoforms (STAT5A/STAT5B), and STAT5 is directly activated by JAK2 downstream of several cytokine receptors and the oncogenic BCR-ABL tyrosine kinase. Using an IL-3-dependent cell...

The hallmark of Philadelphia chromosome positive (Ph(+)) leukemia is the BCR/ABL kinase, which is successfully targeted by selective ATP competitors. However, inhibition of BCR/ABL alone is unable to eradicate Ph(+) leukemia. The t(9;22) is a reciprocal translocation which encodes not only for the der22 (Philadelphia chromosome) related BCR/ABL, but also for der9 related ABL/BCR fusion proteins...

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...

We report a case of an asymptomatic 39-year-old male who was incidentally found to have a white blood cell count of 15 000/mm(3) associated with a positive BCR-ABL/t(9;22)(q34;q11) chromosomal translocation detected in 51/300 of cells by FISH and RT-PCR from peripheral blood. Within the next 3 months, leukocytosis spontaneously subsided; however, BCR-ABL by RT-PCR and FISH was persistent both i...

The chimeric oncogene BCR/ABL, which is the product of reciprocal translocation between chromosomes 9 and 22, is a known molecular marker of chronic myeloid leukemia (CML), and is related to the major factors involved in leukemogenesis. Some previous studies have also reported the presence of this oncogene in peripheral blood cells of healthy individuals. In this study, we investigated the pres...

Chronic myelogenous leukemia (CML) is a type of leukemia originating from hematopoietic stem cells characterized by unregulated proliferation of myeloid cells. Leukemic cells carry the chromosome, a translocation between one chromosome 9 and one chromosome 22. This chromosome has the fusion gene which consists of fragments of the breakpoint cluster region (BCR) and abelson murine leukemia (ABL)...

The Philadelphia (Ph1) chromosome in chronic myelogenous leukemia (CML) involves reciprocal translocation of the bcr gene and the c-abl oncogene. The fused bcr/abl gene is transcribed into two types of chimeric mRNA. By means of a combined method of S1 nuclease protection and polymerase chain reaction, we amplified sequences representative of the chimeric bcr/abl transcripts. Only 5 micrograms ...

HE PHILADELPHIA (Ph) chromosome was the first T chromosomal abnormality associated with a specific malignant disease in humans, namely chronic myeloid leukemia (CML).’ Later it was identified as one partner in a reciprocal translocation between chromosomes 9 and 22, referred to as t(9;22)(q34;q11).2 We know now that this translocation results in the formation of two hybrid genes, BCR-ABL on the...