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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 815-819
Molecular quantitation of minimal residual disease in
acute myeloid leukemia with t(8;21) can identify patients in durable
remission and predict clinical relapse
K. Tobal,
J. Newton,
M. Macheta,
J. Chang,
G. Morgenstern,
P. A. S. Evans,
G. Morgan,
G. S. Lucas, and
J. A. Liu Yin
From the University Department of Hematology, Manchester Royal
Infirmary, Manchester, United Kingdom (UK); Christie Hospital,
Manchester, UK; and Leeds General Hospital, Leeds, UK.
One of the most common translocations in acute myeloid leukemia
(AML) is the t(8;21), which produces the fusion gene AML1-MTG8. We have developed a sensitive competitive reverse
transcriptase-polymerase chain reaction (RT-PCR) assay for
AML1-MTG8 transcripts, coupled with a competitive RT-PCR for
the ABL transcript as a control to accurately estimate the
level of amplifiable RNA. We have shown that AML1-MTG8 and
ABL transcripts have equal degradation rates. Thus, this method
is useful for multicenter studies. We studied 25 patients with t(8;21)
AML by means of serial analysis done on bone marrow (BM) and peripheral
blood (PB) samples from 21 patients. Our analysis showed that, in
general, a successful induction chemotherapy produces a reduction of 2 to 3 log in the level of AML1-MTG8, followed by a further 2 to
3 log after consolidation/intensification chemotherapy. Levels up to
1 × 103 and 1 × 102 molecules/µg of
RNA in BM and PB, respectively, were compatible with durable remission.
On the other hand, 5 patients with levels of 0.71 × 105
to 2.27 × 105 molecules/µg of RNA in BM and
2.27 × 103 to 2.27 × 104 molecules/µg
of RNA in PB had hematologic relapse within 3 to 6 months. Our data
indicate that serial quantitation of AML1-MTG8 transcripts is
useful in identifying patients at high risk of relapse and may offer an
opportunity for clinical intervention to prevent hematologic relapse.
This approach was applied successfully in a patient who had an
allogeneic BM transplantation. We also suggest that PB may be used an
alternative to BM for quantitating AML1-MTG8 transcripts.
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