Detection and quantitation of the CBFbeta/MYH11 transcripts associated with the inv (16) in presentation and follow-up samples from patients with AML
Evans, P.A.; Short, M.A.; Jack, A.S.; Norfolk, D.R.; Child, J.A.; Shiach, C.R.; Davies, F.; Tobal, K.; Liu Yin, J.A.; Morgan, G.J.
Leukemia 11(3): 364-369
1997
ISSN/ISBN: 0887-6924 PMID: 9067575 Document Number: 481621
We have developed a competitor-based RT-PCR technique which will detect and quantitate the CBF-beta/MYH11 transcripts associated with inv(16)(q22;p13) and have used it to study presentation and follow-up samples of acute myeloid leukaemia (AML). The levels of the leukaemia-specific transcripts are expressed as a ratio to a ubiquitously expressed mRNA species (Abl) which controls for RNA degradation. This technique has been applied to 75 consecutive patients presenting with either de novo AML or tMDS; 6/75 patients analysed were positive for the inv(16), all were confirmed by conventional cytogenetics. The inv(16) has a strong association with M4Eo, but we found only 2/6-positive patients to have this diagnosis (two patients with M2, one patient M1 and one patient had MDS). At presentation the levels of CBF-beta/MYH11 transcripts were 0.1-10/Abl transcript (mean 3.3/Abl transcript). Seventeen follow-up samples were available on 5/6 of these patients, and on two further patients in whom stored material was available. Following the first cycle of chemotherapy the level of transcripts was at least 10-2 lower (0.1-10 times 10-2/abl transcript) than their presentation sample. Subsequent samples on these patients when in remission gave transcript levels in the range (1.0 times 10-4-2 times 10-3/abl transcript), and three long-term follow-up samples were negative. We have developed a quantitative test which opens the possibility of predicting relapse by detecting changes in the numbers of leukaemia-specific transcripts.