title: Frequent aberration of FHIT gene expression in acute leukemias.
abstract: We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.
authors.affiliation: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwai
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.forename: N
authors.initials: N
authors.lastname: Nakazawa
authors.forename: M
authors.initials: M
authors.lastname: Taniwaki
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authors.initials: T
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Sonoda
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: H
authors.initials: H
authors.lastname: Azuma
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: T
authors.initials: T
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Kikuta
authors.forename: K
authors.initials: K
authors.lastname: Asami
authors.forename: I
authors.initials: I
authors.lastname: Sekine
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: J
authors.initials: J
authors.lastname: Mimaya
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Miyake
authors.forename: Y
authors.initials: Y
authors.lastname: Takaue
authors.forename: A
authors.initials: A
authors.lastname: Iwai
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D017766:Acid Anhydride Hydrolases; D000208:Acute Disease; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics; D007948:Leukemia, Monocytic, Acute / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase