Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.
Tobal, K Newton, J Macheta, M Chang, James Morgenstern, Godfrey R Evans, P A Morgan, Gareth J Lucas, Guy S Liu Yin, J A
Tobal, K
Newton, J
Macheta, M
Chang, James
Morgenstern, Godfrey R
Evans, P A
Morgan, Gareth J
Lucas, Guy S
Liu Yin, J A
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Abstract
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 x 10(3) and 1 x 10(2) molecules/microg of RNA in BM and PB, respectively, were compatible with durable remission. On the other hand, 5 patients with levels of 0.71 x 10(5) to 2.27 x 10(5) molecules/microg of RNA in BM and 2.27 x 10(3) to 2.27 x 10(4) molecules/microg 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.
Description
Date
2000-02-01
Publisher
Collections
Keywords
Acute Myeloid Leukaemia
Cancer Recurrence
Residual Cancer
Biological Tumour Markers
Cancer Recurrence
Residual Cancer
Biological Tumour Markers
Type
Article
Citation
Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse. 2000, 95 (3):815-9 Blood