Pattern of FHIT gene expression in normal and leukaemic cells.

Abstract

Chromosomal aberrations and inactivation of tumour suppressor genes are frequent in acute leukaemia. To determine whether the FHIT gene is involved in the development of leukaemia, we examined the FHIT transcript in 65 leukaemia cell lines, 5 fresh acute leukaemia patients at diagnosis and in complete remission, normal peripheral blood lymphocytes obtained from 14 healthy volunteers and Epstein-Barr (EB) virus transformed 5 B-cell lines (EB-lines), using nested reverse transcription-polymerase chain reaction and direct sequencing. The transcripts were classified into 4 patterns: pattern I revealed the normal transcripts only, pattern II the altered transcripts in addition to the normal transcripts, pattern III the altered transcripts without the normal transcripts and pattern IV an absence of normal and altered FHIT transcripts. Nineteen cell lines were classified as pattern I, 32 as pattern II, 2 as pattern III and 12 as pattern IV. The frequency of loss of FHIT expression (pattern III or IV) varied in each type of leukaemia cell line; the order ranked from the highest incidence was acute myeloid leukaemia (AML), T-cell acute lymphoblastic leukaemia (T-ALL), B-precursor ALL, B-ALL, and chronic myeloid leukaemia (CML). No genomic rearrangement was found in any samples examined. All of 5 patients showed same pattern II FHIT transcripts at 2 different stages of the disease. All normal peripheral blood lymphocytes and EB-lines were classified as pattern I or II. Our results suggested that patterns III and IV of FHIT transcripts might be associated with the development of a subset of leukaemia, while pattern II which has so far been reported as an aberrant transcript in varieties of malignant tumours might not be associated with leukaemogenesis.