Heterogenic molecular basis for loss ofABL1-BCRtranscription: Deletions in der(9)t(9;22) and variants of standard t(9;22) inBCR-ABL1-positive chronic myeloid leukemia

Publisher Website
Google Scholar
Abstract
The objective of this study was to characterize the ABL1‐BCR fusion gene in 76 BCR‐ABL1‐positive chronic myeloid leukemia (CML) patients regarding expression as well as genomic status, to assess the frequency of ABL1‐BCR gene deletion in these patients, which has been reported to be an adverse prognostic factor in Philadelphia chromosome‐positive CML. Patients were analyzed for ABL1‐BCR 1b‐b3 and/or 1b‐b4 transcription by RT‐PCR analysis. ABL1‐BCR gene status was analyzed by FISH in 16 CML patients with no ABL1‐BCR transcript. FISH revealed a partial or total deletion of the ABL1‐BCR gene in 9/16 and localized the 5′ portion of ABL1 and the 3′ portion of BCR at separated loci in 5/16 patients. The latter FISH pattern resulted from a nonreciprocal translocation in two and a complex translocation in three individuals. In 2/16 patients, FISH could not exclude an intact ABL1‐BCR fusion gene. Thus, most CML patients without ABL1‐BCR transcript could be characterized cytogenetically to belong to two major subgroups: a silent ABL1‐BCR gene was attributed to a deletion in der(9)t(9;22) in 56% of the investigated patients or to variants of a standard t(9;22) (∼ 31%). Conversely, none of the 50 patients with an ABL1‐BCR transcript exhibited a variant t(9;22) in GTG‐banding analysis. Thus, genomic aberrations such as deletions or complex genomic rearrangements are the basic and most frequent cause for ABL1‐BCR RNA negativity in CML. The heterogeneity of the underlying molecular mechanisms may explain divergent clinical implications described for patients with an ABL1‐BCR deletion and those with no ABL1‐BCR transcript.

This publication has 20 references indexed in Scilit: