Background and Objective, ALL1 gene rearrangements are frequently found in
secondary acute leukemias (ALs), A site-specific cleavage of the ALL1 gene
in a consensus sequence for topoisomerase II recognition has been considere
d to be the initial step leading to ALL1 rearrangement and subsequent thera
py-related AL, The aim of the present study was to evaluate this cleavage i
n our patients, to analyze whether it is a laboratory-produced artefact and
to check whether it persists or causes a real ALL1 gene rearrangement at r
elapse,
Design and Methods, We studied ALL1 rearrangement in 74 cases of AL before
treatment by Southern blot avoiding room temperature exposure or delay in p
rocessing the samples which could produce ALL1 cleavage. DNA was available
for two cases with ALL1 cleavage; it was analyzed by three different Southe
rn blots in one and two in the other, One case with ALL1 cleavage was also
studied in relapse.
Results. The presence of the cleavage of the ALL1 DNA was found in 3 of 74
(4%) patients. Two of these three patients had the ALL1 cleavage in three a
nd two different analyses, One case was positive for ALL1 cleavage at diagn
osis, but negative for both ALL1 cleavage and ALL1 rearrangement at relapse
,
Interpretation and Conclusions, The fact that a constant-pattern was obtain
ed from the same patients in different DNA preparations, supports the notio
n that ALL1 cleavage is not a laboratory artefact, The absence of the cleav
age in a sample from a relapsed patient suggests that the subclone with the
ALL1 cleavage, in this case, did not play a clear role in the pathogenesis
of disease recurrence. (C) 1999, Ferrata Storti Foundation.