Derivative chromosome 9 deletions in chronic myeloid leukemia are associated with loss of tumor suppressor genes.

ABSTRACT

It has recently been postulated that the absence of a single tumor suppressor gene (TSG) allele can provide a selective advantage for an emerging tumor cell. We have characterized the precise extension of the deletion on der(9) in 20 chronic myeloid leukemia (CML) cases using FISH analysis with an appropriate set of BAC/PAC probes to attempt a better definition of TSGs encompassed by these genomic deletions. Chromosome 9 deletions on the der(9) were detected in 15 (75%) cases; the TSG PTGES gene was lost in 11 (73%) cases. Chromosome 22 deletions on der(9) were found in 18 (90%) of the analysed cases; two TSGs were found located inside the deleted sequences of chromosome 22 SMARCB1 and GSTT1. These TSGs were found deleted in 16 (89%) cases bearing deletions of chromosome 22. Fourteen (70%) patients were treated with IFN-alpha therapy 12 did not obtain complete haematologic remission (CHR) and 2 were not evaluable for response. Therefore, the patients did not respond to the IFN-alpha treatment started Glivec obtaining CHR and major cytogenetic response (MCR). The observation that deletions on der(9) are associated with the loss of TSGs suggests their possible involvement in the CML outcome, mediated by a haplo-insufficiency mechanism.