Background: The Philadelphia chromosome (Ph) characterized by t (9; 22) (q34; q11.2) is a reciprocal translocation giving rise to a chimeric BCR-ABL fusion gene. Incidence of Ph chromosome is over 98% in Patients with Chronic Myeloid Leukemia (CML) and around 20% in acute lymphoblastic leukemia (ALL). The finding of this fusion gene is essential for diagnosis of CML by detection of various fusi...

Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, progression. We recently reported that signal-transducing adaptor protein 1 (STAP-1) upregulated CML stem cells (LSCs) functions to reduce apoptosis LSCs upregulating STAT5-d...

with the present specifications for clasification, 95% of chronic myelogeneous leukaemia (cml) cases have the t(9;22), which brings the abl oncogene to the bcr region and results in a hybrid gene bcr/abl. there may be involvement of other chromosomes in 2-10%, and secondry or additional chromosome abberations may present in 60-80% during the progression of the disease. in the majority of the re...

The Abl family of nonreceptor tyrosine kinases consists of two related proteins, c-Abl and Abl-related gene (Arg). Activated forms of the Abl kinases (BCR-Abl, Tel-Abl, and Tel-Arg) induce the development of human leukemia; it is not known, however, whether Abl kinases are activated in solid tumors or whether they contribute to tumor development or progression. Previously, we showed that Abl ki...

Using human acute leukemia HL-60/Bcr-Abl (with ectopic expression of p185 Bcr-Abl) and K562 cells (with endogenous expression of p210 Bcr-Abl) subjected to a continuous selection pressure of up to 1.0 micro M Gleevec (imatinib mesylate, STI-571), we have isolated Gleevec-resistant K562 R (+Bcr-Abl), K562 R (-Bcr-Abl), and HL-60/Bcr-Abl R cells, which display disparate level and activity of Bcr-...

The bcr-abl oncogene plays a critical role in the pathogenesis of chronic myelogenous leukemia (CML). The fusion of Bcr sequences to Abl constitutively activates the Abl protein tyrosine kinase. We have recently shown that expression of Bcr-Abl in bone marrow cells by retroviral transduction efficiently induces in mice a myeloproliferative disease resembling human CML and that Abl kinase activi...

The Bcr-Abl oncoprotein is the primary causative factor in Philadelphia chromosome-associated leukemias. The activated tyrosine kinase of the Bcr-Abl oncoprotein is the primary driving force behind its oncogenic activity. We report here that a deleted form of Bcr [Bcr(64-413)], encompassing the Abl SH2 binding domains of Bcr, reduced the phosphotyrosine content of c-Abl and Bcr-Abl within cells...

introduction: reverse transcriptase-polymerase chain reaction (rt-pcr) assay is a useful tool for the detection of fusion transcript resulting from specific chromosomal translocation of the leukemia cells. a specific chromosomal abnormality, the philadelphia chromosome (ph), is present in 90% to 95% of cml patients.the aberration results from a reciprocal translocation between chromosome 9 and ...

Despite promising clinical results from imatinib mesylate and second-generation ABL tyrosine kinase inhibitors (TKIs) for most BCR-ABL(+) leukemia, BCR-ABL harboring the mutation of threonine 315 to isoleucine (BCR-ABL/T315I) is not targeted by any of these agents. We describe the in vitro and in vivo effects of AT9283 (1-cyclopropyl-3[5-morpholin-4yl methyl-1H-benzomidazol-2-yl]-urea), a poten...