Significance of FHIT expression in chronic myelogenous leukemia

Loss or reduced expression of the fragile histidine triad (FHIT) gene, a tu mor suppressor gene localized at chromo some 3p14.2, is common in several s olid and hematological cancers and has been associated with tumor progressi on and worse prognosis. The role of the FHIT gene in the pathogenesis of ch ronic myelogenous leukemia (CML) or its progression from a chronic phase to the accelerated and blastic phases is not known. The aim of this study was to evaluate whether Fhit protein expression is altered in CML, and whether it plays any role in CML progression, disease responsiveness to therapy, o r prognosis. A total of 195 patients with Philadelphia chromosome-positive CML were evaluated, including 129 patients in early chronic phase (time fro m diagnosis to study, 12 months or less), 30 patients in late chronic phase , and 36 patients in the accelerated and blastic phases. The levels of cell ular Fhit protein expression were determined using Western blot analysis an d solid-phase RIA and compared to the levels in 31 normal marrows. The medi an Fhit expression in normal marrows was assigned a value of 1, and the lev els in CML samples were normalized to the median of the normal control. Fhi t levels in CML samples were evaluated in relation to CML phase and patient characteristics and prognosis in the early chronic phase. The median Fhit value in CML samples was 0.89 (range, 0.34-2.62), Eight of the 195 (4%) CML samples showed Fhit levels <0.5 and lacked detectable Fhit protein by West ern blot. There was no difference in the levels of Fhit expression by diffe rent CML phases. In early chronic phase, reduced Fhit expression tended to be associated,vith leukocytosis (P = 0.04) and lower platelet counts (P = 0 .01), but not with poorer-risk groups. No differences in response to IFN-al pha therapy or in survival were observed by different Phit levels, Lack of Fhit protein expression was detected in 4% of CML cases, and reduced expres sion occurred in a subpopulation of patients. However, reduced Fhit express ion is not associated,vith progression, response to therapy, or prognosis i n CML.