CBFβ/MYH11 Rearrangement in M4Eo with Inversion 16: A Novel Marker for Diagnosis of Minimal Residual Disease by RT-PCR

Abstract

The inversion of chromosome 16(pl3-q22) is a characteristic cytogenetic marker for acute myelogenous leukemia subtype M4Eo. Recently the fusion gene product of this pericentric translocation was characterized. The CBFβ gene is translocated from 16q in the region of MYH11, a smooth muscle gene on the short arm of chromosome 16. This may result in altered regulation of transcription and subsequent leukemic transformation. We wanted to evaluate the potential of this rearrangement as a new target for minimal residual disease (MRD) diagnosis, which is routinely carried out by RTPCR. BM and PB samples from six patients with M4Eo were analyzed at diagnosis, in clinical remission, and during relapse. The detection of inv(16) always correlated with a CBFβ/MYHll rearrangement. Five patients showed a type A transcript and one patient a type B fusion. PCR negativity in remission was observed in one patient who has been relapse-free for more than 20 months. Samples from three other patients investigated in clinical and cytogenetic remision remained PCR-positive; two of them have relapsed so far. We conclude that the CBFβ/MYH11 rearrangement is highly sensitive, and residual leukemia can be detected during remission. The value of for MRD evaluation needs confirmation in a larger study of prospectively analyzed patients.