DELETION OF GENE FOR MULTIDRUG-RESISTANCE IN ACUTE MYELOID-LEUKEMIA WITH INVERSION IN CHROMOSOME-16 - PROGNOSTIC IMPLICATIONS

Acute myeloid leukaemia (AML) associated with an inversion in chromosome 16 has a relatively favourable prognosis. The AML subclass most commonly associated with this chromosomal abnormality is acute myelomonocytic leukaemia with abnormal eosinophils. In some AML patients with inversion 16 the chromosomal lesion results in deletion of MRP, the gene for multidrug resistance associated protein. This gene is proximal to the primary breakpoint and loss of its function may play a key role in determining the favourable outcome in inversion 16 AML. We have demonstrated deletion of MRP by in situ hybridisation, by gene dosage studies and by studying loss of heterogeneity of a flanking microsatellite marker. Among 13 AML patients with inversion 16 MRP deletion was detected in 5 while 7 had no deletion. Deletion of MRP gene was associated with longer time from diagnosis until death or relapse from complete remission (p=0.007). These findings provide important insight into the biology of inversion 16 leukaemia and suggest that MRP deletion, as detected by molecular analysis, may,have a key role in determining outcome in patients with inversion 16 AML.