Decreased or Altered Expression of the FHIT Gene in Human Leukemias

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Abstract
The FHIT (fragile histidine triad) gene on chromosome 3p14 is a candidate tumor suppressor gene, and its transcripts are shown to be abnormal in several human cancers. We examined 40 leukemia samples for the alterations of FHIT transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing. Intact FHIT mRNA was not detected in two patients with acute myeloid leukemia (AML) and in one patient with chronic lymphocytic leukemia (CLL). The three cases expressed only an aberrant FHIT mRNA lacking exons 3 to 6 (FHIT Δ3-6 mRNA), which could encode a polypeptide of 13 amino acids. Southern blot analysis on two samples from these cases showed no rearrangements of the FHIT gene. Although intact FHIT mRNA was detected as the main band in the remaining 37 samples, 33 of them (14 of 14 AML, 11 of 13 chronic myeloid leukemia, five of five acute lymphocytic leukemia, and three of five CLL) expressed aberrant FHIT Δ3-6 mRNA. We barely detected the FHIT Δ3-6 mRNA in only one of 25 normal control samples. Our results suggest that loss of the normal FHIT function may be involved in the genesis of at least some human leukemias and that expression of aberrant FHIT transcripts is rather specific and frequent in leukemia samples.