Philadelphia-positive chronic myelogenous leukemia with breakpoint 5? of the breakpoint cluster region but within the bcr gene

Abstract

We report on the first Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) characterized by a rearrangement within the 5' part of the bcr gene on chromosome 22, but outside the restricted breakpoint cluster region. In situ hybridization studies revealed a translocation of the c-abl oncogene to the Ph chromosome and Northern blot analysis identified a chimeric 8 kb bcr/abl RNA transcript in leukemic cells. These data suggest that 1. less bcr coding sequences than previously assumed may be essential for the putative transforming activity of the rearranged bcr/abl gene and 2. the bcr probes currently used for diagnostic purposes could miss Ph-positive CML cases.

Analysis of molecular breakpoint and m‐RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival

“…We were unable to identify any RNA transcript in this case, either b2a2, b3az or el a2. This is similar to a report by Negrini et a1 (1992) and has also been reported in small numbers in other series (Saglio et al, 1988Bartram et al, 1988;Min et al, 1990;Selleri et al, 1990;. Correlation of RNA transcript with genomic breakpoint sites shows that one-third of zone 3 cases have the b2a2 transcript and two-thirds the b3a2 transcript.…”

Detection and quantification of residual disease in chronic myelogenous leukemia

“…37,38 False-negative results may arise because the rearranged band is too large, too small or coincidentally exactly the same size as the normal allele, as a result of partial deletion of BCR sequences on the translocated allele 39 or of rare variants that have breakpoints outside the M-bcr. 14,40,41 False-positive or -negative results are, however, rare. 36 After therapy Southern blot analysis allows quantification of the proportion of cells with BCR rearrangement compared to all cells investigated.…”

Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML

“…negative CML patient described by Bartram et al [40], which had a breakpoint in the bcr gene located 5' of the BCR region but 3' of the region described by Selleri et al [38,39] 3) In 20 out of 25 cases of aCML, no BCR breakpoint was detected. The five exceptions with a BCR breakpoint were all reported by the same research group [41,42].…”