Pattern of FHIT gene expression in normal and leukaemic cells

Chromosomal aberrations and inactivation of tumour suppressor genes are fre quent in acute leukaemia. To determine whether the FHIT gene is involved in the development of leukaemia, we examined the FHIT transcript in 65 leukae mia cell lines, 5 fresh acute leukaemia patients at diagnosis and in comple te 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 reve aled the normal transcripts only, pattern II the altered transcripts in add ition to the normal transcripts, pattern III the altered transcripts withou t the normal transcripts and pattern IV an absence of normal and altered FH IT transcripts. Nineteen cell lines were classified as pattern I, 32 as pat tern II, 2 as pattern III and 12 as pattern IV. The frequency of loss of FH IT expression (pattern III or IV) varied in each type of leukaemia cell lin e; 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 i n any samples examined. All of 5 patients showed same pattern II FHIT trans cripts at 2 different stages of the disease. All normal peripheral blood ly mphocytes and EB-lines were classified as pattern I or II. Our results sugg ested 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 fa r been reported as an aberrant transcript in varieties of malignant tumours might not be associated with leukaemogenesis. (C) 1999 Wiley-Liss, Inc.