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October 1999, Volume 13, Number 10, Pages 1519-1524
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Original manuscript
Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR
G Mitterbauer1, C Zimmer1, C Fonatsch2, O A Haas3, R Thalhammer-Scherrer4, I Schwarzinger4, P Kalhs5, U Jaeger6, K Lechner6 and C Mannhalter1

1Department of Laboratory Medicine, Division of Molecular Biology, Vienna, Austria

2Institute of Medical Biology, University of Vienna, Vienna, Austria

3Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria

4Department of Laboratory Medicine, Division of Hematology, Vienna, Austria

5Department of Medicine I, Bone Marrow Transplantation Unit, Vienna, Austria

6Department of Medicine I, Division of Hematology and Hemostaseology, Vienna, Austria

Correspondence to: G Mitterbauer, Department of Laboratory Medicine, Division of Molecular Biology, University Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria; Fax: 43 1 40400 2097

Abstract

Twenty-seven patients with AML and MLL gene rearrangement were analyzed by a reverse transcriptase polymerase chain reaction (RT-PCR) for the MLL-AF9 translocation. The MLL-AF9 fusion transcript was detected in six patients. In five patients, the breakpoint of the AF9 gene was located within the recently described site A; in one patient, a novel breakpoint (AF9 site D) mapped to a position 377 bp 3' of site A. Five patients could be serially monitored for a period of 4-23 months. Two patients became two-step PCR negative in bone marrow and peripheral blood. Molecular remission was achieved rapidly after one cycle of induction chemotherapy. Both patients are in continuous complete remission (CR) at 22 and 15 months, respectively. Two patients who had achieved hematological CR did not become PCR negative and MLL-AF9 fusion transcripts were detectable in all samples after induction and consolidation chemotherapy. One patient relapsed 5 months after achieving CR. The other patient received allogeneic bone marrow transplantation from an HLA-identical sibling 2 months after achieving hematological CR and became PCR negative 4 weeks after transplantation. In the fifth patient, hematological CR could not be achieved with two cycles of intensive induction chemotherapy, and MLL-AF9 transcripts were present in all samples tested. Our data indicate that MLL-AF9 RT-PCR is specific for the t(9;11) translocation. PCR negativity can be achieved in responding patients already 1 month after induction chemotherapy. The fast reduction of MLL-AF9 positive blast cells below the detection limit of RT-PCR seems to be a prerequisite for long-term CR. The results of RT-PCR may be useful for treatment decisions (eg BMT).

Keywords

acute myeloid leukemia; t(9; 11)(p22; q23); MLL-AF9; RT-PCR; minimal residual disease (MRD)

Received 29 April 1999; accepted 24 June 1999
October 1999, Volume 13, Number 10, Pages 1519-1524
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