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
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).