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FHIT gene transcript alterations occur frequently in myeloproliferative and myelodysplastic diseases

Twenty-five primary biopsy samples, obtained from patients diagnosed with chronic/acute myeloproliferative disorders, myelodysplastic disorders, in addition to seven cell lines established from patients with leukemias arrested at different stages of myeloid differentiation, were examined for alterations in an alternatively spliced form of the FHIT gene. Transcript alterations of this gene were detected in 80% of the primary biopsies and in two of the cell lines. Reverse transcription PCR (RT-PCR) detected deletions of one or more specific exons in the translated or untranslated portion of the FHIT gene. Point mutations in exons 3, 4, and 5 of the FHIT gene were also detected in 4 patients by single stranded conformational PCR analysis. Transcript alterations were detected in all primary hematopoietic samples which contained chromosome abnormalities, as well as, in hematopoietic disorders which did not show alterations of the 3p14 region. These findings suggest FHIT gene involvement in the transformation of hematopoietic stem cells to leukemia.