title: Clinical significance of fragile histidine triad gene expression in adult acute lymphoblastic leukemia.
abstract: The FHIT (fragile histidine triad) gene, which is located on 3p14.2 and believed to be a tumor suppressor gene, has been reported to lose its expression in several solid tumors and hematologic malignancies, including acute lymphoblastic leukemia (ALL). The clinical relevance of the loss of FHIT expression in ALL is not known. We used western blot and solid-phase radioimmunoassay (RIA) to analyze Fhit protein expression in 90 patients with ALL. Eighteen (20%) of the tested patients had severely reduced Fhit protein (undetectable by western blot), and 43 patients (47%) had levels lower than those detected in normal bone marrows. Interestingly, seven patients (8%) expressed very high levels (>two-fold the level detected in normal bone marrow). A parallel pattern of FHIT RNA expression was also observed. Of the 90 patients, 39 received induction therapy consisting of hyper-CVAD (hyperfractionated cyclophosphamide, vencristine, adriamycine, and dexamethasone) and were followed in our institution. Patients with low Fhit protein levels showed no statistically significant difference in survival or complete remission duration (CRD) from patients with normal levels (P=0.12 and 0.24, respectively). Our study confirms that FHIT is aberrantly expressed in ALL, but suggests it does not have a role as a prognostic factor. Studies with large numbers of patients and evaluation of the mechanisms of FHIT function in ALL are needed.
authors.affiliation: Department of Hematopathology, Box 72, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4095, USA. malbitar@mdacc.tmc.edu
authors.forename: M
authors.initials: M
authors.lastname: Albitar
authors.forename: T
authors.initials: T
authors.lastname: Manshouri
authors.forename: C
authors.initials: C
authors.lastname: Gidel
authors.forename: C
authors.initials: C
authors.lastname: Croce
authors.forename: S
authors.initials: S
authors.lastname: Kornblau
authors.forename: S
authors.initials: S
authors.lastname: Pierce
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D017931:DNA Primers; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase