Detection and quantitation of the CBFbeta/MYH11 transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML

Leukemia. 1997 Mar;11(3):364-9. doi: 10.1038/sj.leu.2400578.

Abstract

We have developed a competitor-based RT-PCR technique which will detect and quantitate the CBFbeta/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 CBFbeta/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 x 10(-2)/abl transcript) than their presentation sample. Subsequent samples on these patients when in remission gave transcript levels in the range (1.0 x 10(-4) - 2 x 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.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Child
  • Chromosome Inversion*
  • Chromosomes, Human, Pair 16*
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism*
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / biosynthesis*
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction / methods
  • Transcription, Genetic

Substances

  • CBFbeta-MYH11 fusion protein
  • Oncogene Proteins, Fusion