ABERRANT TRANSCRIPTS OF THE FHIT GENE ARE EXPRESSED IN NORMAL AND LEUKEMIC HEMATOPOIETIC-CELLS

Deletions and apparent transcriptional abnormalities of the FHIT gene at 3p14.2 have recently been reported in a wide variety of solid tumou rs. To determine whether lesions of this gene also occur in leukaemia, we have analysed a total of 97 patients (chronic myeloid leukaemia, C ML, in chronic phase or blast crisis, n = 71, de novo acute leukaemia, n = 26) and 16 normal individuals, intact FHIT transcripts from all c ases were amplified using RT-PCR. In addition, smaller size bands that were less intense than the full-length products were amplified from s everal samples from patients with leukaemia and also from normal leuco cytes. Sequencing of the small products revealed that they were derive d from FHIT transcripts lacking whole exons. Using single-strand confo rmation polymorphism analysis, no mutations in the coding sequence wer e detected in any patient, Furthermore, loss of heterozygosity was not seen in any of 36 informative patients at D3S1300 or D3S1481, markers located within the FHIT locus. We conclude that the FHIT gene and oth er uncharacterized tumour-suppressor genes at 3p14.2 are unlikely to b e involved in the pathogenesis of acute leukaemia or progression of CM L from chronic phase to blast crisis. Moreover, low-abundance FHIT tra nscripts that lack whole exons are not specific to malignant cells and should not be taken as evidence of an abnormality in the absence of d emonstrable genomic DNA lesions.