Clinical significance of fragile histidine triad gene expression in adult acute lymphoblastic leukemia

The FHIT (fragile histidine triad) gene, which is located on 3p14.2 and bel ieved to be a tumor suppressor gene, has been reported to lose its expressi on in several solid tumors and hematologic malignancies, including acute ly mphoblastic leukemia (ALL). The clinical relevance of the loss of FHIT expr ession in ALL is not known. We used western blot and solid-phase radioimmun oassay (RIA) to analyze Fhit protein expression in 90 patients with ALL. Ei ghteen (20%) of the tested patients had severely reduced Fhit protein (unde tectable by western blot), and 43 patients (47%) had levels lower than thos e detected in normal bone marrows. Interestingly, seven patients (8%) expre ssed 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 pa tients, 39 received induction therapy consisting of hyper-CVAD (hyperfracti onated cyclophosphamide, vencristine, adriamycine, and dexamethasone) and w ere followed in our institution. Patients with low Fhit protein levels show ed no statistically significant difference in survival or complete remissio n duration (CRD) from patients with normal levels (P = 0.12 and 0.24, respe ctively). 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 A LL are needed. (C) 2001 Elsevier Science Ltd. All rights reserved.