Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR

Citation
G. Mitterbauer et al., Monitoring of minimal residual leukemia in patients with MLL-AF9 positive acute myeloid leukemia by RT-PCR, LEUKEMIA, 13(10), 1999, pp. 1519-1524
Citations number
40
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA
ISSN journal
08876924 → ACNP
Volume
13
Issue
10
Year of publication
1999
Pages
1519 - 1524
Database
ISI
SICI code
0887-6924(199910)13:10<1519:MOMRLI>2.0.ZU;2-G
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 rec ently described site A; in one patient, a novel breakpoint (AF9 site D) map ped to a position 377 bp 3' of site A. Five patients could be serially moni tored for a period of 4-23 months. Two patients became two-step PCR negativ e in bone marrow and peripheral blood. Molecular remission was achieved rap idly after one cycle of induction chemotherapy. Both patients are in contin uous complete remission (CR) at 22 and 15 months, respectively. Two patient s who had achieved hematological CR did not become PCR negative and MLL-AF9 fusion transcripts were detectable in all samples after induction and cons olidation chemotherapy. One patient relapsed 5 months after achieving CR. T he other patient received allogeneic bone marrow transplantation from an HL A-identical sibling 2 months after achieving hematological CR and became PC R negative 4 weeks after transplantation. In the fifth patient, hematologic al CR could not be achieved with two cycles of intensive induction chemothe rapy, 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 in duction chemotherapy. The fast reduction of MLL-AF9 positive blast cells be low 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).