In chronic myelogenous leukemia (CML) the reciprocal translocation resulting in the Philadelphia chromosome (Ph1) leads to the formation of a chimeric transcriptional unit carrying both c-abl and bcr genetic information whose transcript is a new fused mRNA of 8.5-kilobases (kb) and whose translational product is a 210-kD phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML. Twenty patients affected by Ph1-positive CML were studied by Southern blot analysis with bcr. Unexpectedly, in three Ph1-positive patients, the breakpoint of chromosome 22 was located neither inside the bcr region nor 5' to it. Northern blot analysis of the RNAs of two of these patients showed the absence of a detectable 8.5-kb chimeric mRNA. In the third patient a chimeric mRNA was detected by a c-abl cDNA probe but failed to hybridize with a bcr cDNA probe and showed very low hybridization levels with further 5' bcr cDNA probes. The possibility is raised that in CML a breakpoint outside bcr might either still allow the formation of a chimeric mRNA, possibly through alternative splicing mechanisms, or might prevent the transcription of the chimera. In the latter case different molecular events resulting in the formation of a Ph1 chromosome may underlie the same myeloid neoplastic phenotype.
|Anno di pubblicazione:||1987|
|Titolo:||Philadelphia positive chronic myeloid leukemia with 22 breakpoint outside the "beakpoint cluster region" (bcr).|
|Autore/i:||L. SELLERI; F. NARNI; G. EMILIA; A. COLO'; P. ZUCCHINI; D. VENTURELLI; A. DONELLI; U. TORELLI; G. TORELLI.|
|Codice identificativo Scopus:||2-s2.0-0023605155|
|Tipologia||Articolo su rivista|
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