Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia

At diagnosis, clonal gene rearrangement probes [retinoic acid receptor (RAR )-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine gene s (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 15 3 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In a ll cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the case s, respectively, whereas only few cases showed gene rearrangements in the M -bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangemen ts. No worse survival outcome was seen in patients with rearrangements in t he MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrang ements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with g ene rearrangements at diagnosis showed the same kind of rearrangement at re lapse of the disease (n = 12). Our data show that (1) populations with clon al gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at dia gnosis have a prognostic significance for the patients' outcome. Our result s point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify 'poor risk' patients - independently of the karyo type. Moreover, the persistence of clonal cells in the further course of AM L can be studied by gene rearrangement analysis. Copyright (C) 2000 S. Karg er AG, Basel.