Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86644
Title:
Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.
Authors:
Tobal, K; Newton, J; Macheta, M; Chang, James; Morgenstern, Godfrey R; Evans, P A; Morgan, Gareth J; Lucas, Guy S; Liu Yin, J A
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.
Affiliation:
University Department of Hematology, Manchester Royal Infirmary, Manchester, United Kingdom. ktobal@labmed.cmht.nwest.rhs.uk
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
Journal:
Blood
Issue Date:
1-Feb-2000
URI:
http://hdl.handle.net/10541/86644
PubMed ID:
10648391
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorTobal, Ken
dc.contributor.authorNewton, Jen
dc.contributor.authorMacheta, Men
dc.contributor.authorChang, Jamesen
dc.contributor.authorMorgenstern, Godfrey Ren
dc.contributor.authorEvans, P Aen
dc.contributor.authorMorgan, Gareth Jen
dc.contributor.authorLucas, Guy Sen
dc.contributor.authorLiu Yin, J Aen
dc.date.accessioned2009-11-23T10:09:08Z-
dc.date.available2009-11-23T10:09:08Z-
dc.date.issued2000-02-01-
dc.identifier.citationMolecular 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 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid10648391-
dc.identifier.urihttp://hdl.handle.net/10541/86644-
dc.description.abstractOne 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.en
dc.language.isoenen
dc.subjectAcute Myeloid Leukaemiaen
dc.subjectCancer Recurrenceen
dc.subjectResidual Canceren
dc.subjectBiological Tumour Markersen
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshBone Marrow-
dc.subject.meshChromosomes, Human, Pair 21-
dc.subject.meshChromosomes, Human, Pair 8-
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshDisease-Free Survival-
dc.subject.meshHumans-
dc.subject.meshLeukemia, Myeloid, Acute-
dc.subject.meshNeoplasm Recurrence, Local-
dc.subject.meshNeoplasm, Residual-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshRNA, Messenger-
dc.subject.meshRNA, Neoplasm-
dc.subject.meshRemission Induction-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSensitivity and Specificity-
dc.subject.meshTranscription Factors-
dc.subject.meshTranslocation, Genetic-
dc.subject.meshTumor Markers, Biological-
dc.titleMolecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.en
dc.typeArticleen
dc.contributor.departmentUniversity Department of Hematology, Manchester Royal Infirmary, Manchester, United Kingdom. ktobal@labmed.cmht.nwest.rhs.uken
dc.identifier.journalBlooden

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.