G. Marcucci et al., Quantification of CBF beta/MYH11 fusion transcript by Real Time RT-PCR in patients with INV(16) acute myeloid leukemia, LEUKEMIA, 15(7), 2001, pp. 1072-1080
Amplification of the CBF beta /MYH11 fusion transcript by a qualitative rev
erse transcription-polymerase chain reaction (RT-PCR) has been used to defe
ct minimal residual disease (MRD) and assess the risk for disease relapse i
n inv(16)(p13q22) acute myeloid leukemia (AML). This strategy has, however,
produced conflicting results and because of an uncertain predictive value,
its use in the clinical setting cannot be recommended. The objective of th
e current study was to evaluate if quantification by Real Time RT-PCR could
be useful to determine levels of CBF beta /MYH11 fusion transcripts predic
tive of clinical outcome in inv(16)(p13q22) AML at diagnosis or during remi
ssion. Bone marrow (BM) samples from 16 patients with inv(16) AML enrolled
on a German multicenter trial (AML HD93) were analyzed for levels of CBF be
ta /MYH11 fusion transcripts by Real Time RT-PCR at diagnosis (n=14), durin
g remission (n=10) and at relapse (n=6). The CBF beta /MYH11 transcript cop
y number in each sample was normalized to copies of an internal control hou
sekeeping transcript(ie 18S). The copy number measured at diagnosis or rela
pse were 3 to 4 log higher that those measured during remission, following
completion of induction treatment. A high CBF beta /MYH11 transcript copy n
umber at diagnosis had a significant correlation with a high percentage of
BM blasts (Spearman's coefficient = -0.66; P = 0.03), and a borderline corr
elation with a short complete remission (CR) duration (Spearman's coefficie
nt = -0.51; P = 0.07). No difference in levels of CBF beta /MYH11 fusion tr
anscripts measured during intensification therapy was found between patient
s destined to relapse and those who continued in CCR (P = 0.75). Following
completion of the entire chemotherapy program, patients that during CR show
ed a CBF beta /MYH11 fusion transcript copy number > 10 had a significantly
shorter CR duration (P = 0.002) and higher risk for disease relapse (P = 0
.05) than patients with a CBF beta /MYH11 fusion transcript copy number < 1
0. The results of the current study, therefore, suggest that it is possible
to determine in remission samples a threshold of CBF beta /MYH11 transcrip
t copy number above which relapse occurs and below which continuous CR is l
ikely.