Chronic myelogenous leukaemia (CML) is a disease characterized by the presence of the Philadelphia chromosome and the k r d l fusion gene, which result from a reciprocal translocation between chromosomes 9 and 22. Two forms of bcrabl mRNA exist, b3a2 and b2a2, depending upon whether the translocation includes bcr exon 3 or not. The p2 lP-*’ protein, a deregulated tyrosine kinase, is implicated ...

Chomel and colleagues1 recently reported that study of blood or marrow cells from patients in complete cytogenetic remission following treatment with interferon-a or allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) by fluorescence in situ hybridization (FISH) shows appreciable numbers of BCR-ABL–positive cells. They examined 10 patients treated by BMT using RT-PCR...

Chronic Myeloid Leukemia (CML) is effectively treated with Tyrosine Kinase Inhibitors (TKI) such as Imatinib Mesylate (IM) targeted against BCR-ABL, however, several mathematical models and ex vivo-examinations suggested that IM does not eradicate CML stem cells. We previously reported the investigation of residual CML diseases during TKI treatment using FACS-sorting and quantitative RT-PCR of ...

Inhibition of the constitutively active Bcr-abl tyrosine kinase (TK) by STI571 has proven to be a highly effective treatment for chronic myelogenous leukemia (CML). However, STI571 is only transiently effective in blast crisis, and drug resistance emerges by amplification of or development of mutational changes in Bcr-abl. We have screened a family of TK inhibitors of the pyrido [2,3-d]pyrimidi...

We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase–polymerase chain reaction, fluorescence in situ hybridiza...

Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells. After a chronic phase characterized by the isolated presence of the translocation t(9;22), the natural history of the disease includes progression from a benign chronic phase to a rapidly fatal blast crisis, generally accompanied by a range of non-random clonal changes in the malignant clone. This clonal ...

Bcr-Abl, the causative molecular abnormality of CML is known to activate numerous intracellular signaling proteins and pathways. These include ras, raf, phosphatidylinositol 3 -kinase, AKT, STAT (signal transducers and activators of transcription), and various antiapoptotic proteins (1). The activation of these pathways and proteins is dependent on the tyrosine kinase activity of the Bcr-Abl pr...

The recognition of protein kinase C (PKC) as the long soughtafter receptor for the tumor-promoting phorbol esters established the potential role of PKC in carcinogenesis and as a potentially important target for cancer therapeutics (1, 2). PKC is a family of serine/threonine kinases that regulate a variety of cell functions including proliferation, gene expression, cell cycle, differentiation, ...

in complete cytogenetic remission on imatinib mesylate treatment. Blood 2005;105:2093-8. 72. Sherbenou DW, Wong MJ, Humayun A, McGreevey LS, Harrell P, Yang R, et al. Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib. Leukemia 2007;21:489-93. 73. Khorashad JS, Anand M, Marin D, Saunders S, Al-Jabary T, Iqbal A, Margeriso...

Recently, it was shown that both Bcr and Bcr-Abl can interact with xeroderma pigmentosum group B (XPB/ ERCC3), a protein implicated in DNA repair after UVinduced damage. To further analyze the effect of Bcr-Abl on the DNA damage response, we used cell lines stably transfected with the BCR-ABL gene and their parental counterparts (MBA-1 versus MO7E and Bcr-AblT1 versus 4A2 pZAP) and several assa...