The study for loss of bcl-xs expression as a prognostic factor in acute myeloid leukemia.
We reported here abnormal expression profile of the bcl-x gene is associated with the recurrence in acute myelogenous leukemia (AML).The bcl-x gene product exists in two forms, bcl-xl and bcl-xs. The bcl-xl, similar to bcl-2, inhibits apoptosis, whereas bcl-xs counters the effects of bcl-2 and bcl-xl. Mononuclear cells of bone marrow cells were obtained from 50 patients with recurrent AML at diagnosis prior to treatment and during relapse. We investigated the expression of the two isoforms of the bcl-x gene, bcl-xl and bcl-xs. The bcl-xl transcript was detected in all patients at both stages, but the bcl-xs transcript was not detected in six cases at both stages and in seven other cases at relapse (bcl-xs (-) group, n=13). The duration of relapse-free survival (RFS) and overall survival (OS) of the bcl-xs (-) group were significantly shorter than those of the bcl-xs (+) group (RFS: P=0.04; OS: P=0.02). Subsequently, mutation of the bcl-x gene was investigated. No mutation of the bcl-x gene was detected in all patients of both stages. Some refractory leukemic cells which escape chemotherapy-induced apoptosis due to loss of the bcl-xs transcript may continue to proliferate, resulting in the relapse of chemotherapy-resistant leukemia. The examination of the expression status of the bcl-x gene could facilitate the prediction of chemotherapy resistance and the prognosis of patients with refractory AML. The future large study will confirm the present data about loss of bcl-xs gene expression as prognostic factor.
Yamaguchi
Hiroki
H
Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Inokuchi
Koiti
K
Dan
Kazuo
K
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D016019:Survival Analysis; D015996:Survival Rate; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein