Litz C E, Vos J A, Copenhaver C M
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis.
Blood. 1996 Sep 15;88(6):2241-9.
Isolated hypomethylated sites exist in the major breakpoint cluster region (M-bcr) where most Philadelphia chromosome (Ph) breakpoints are located. Twenty of 50 (40%) chronic myeloid leukemia (CML) patients were found to have aberrant hypermethylation of these sites on the rearranged M-bcr when compared with control marrows. The aberrancy correlated strongly with M-bcr breakpoint location; 19 of 20 cases had breakpoints located 5' of the M-bcr Sca I site, and 28 of 30 cases with normal M-bcr methylation had breakpoints located 3' of the M-bcr Sca I site. Sequence analysis of the Ph M-bcr breakpoints failed to find an M-bcr nucleotide position that delineated the transition between abnormally and normally methylated cases, indicating that the translocation of a critical M-bcr sequence was not responsible for the methylation abnormality. In 3 of 8 CML patients, cells without the t(9;22) were found to have abnormally methylated, unrearranged M-bcrs. The data indicate that abnormally methylated rearranged M-bcrs are present in CML cases with Ph breakpoints 5' of the M-bcr Sca I site and that the M-bcr in Ph- cells of patients with CML may also be abnormally methylated.
孤立的低甲基化位点存在于主要断裂点簇区域（M-bcr），大多数费城染色体（Ph）断裂点都位于该区域。与对照骨髓相比，50例慢性髓性白血病（CML）患者中有20例（40%）在重排的M-bcr上这些位点存在异常高甲基化。这种异常与M-bcr断裂点位置密切相关；20例中有19例的断裂点位于M-bcr Sca I位点的5'端，30例M-bcr甲基化正常的病例中有28例的断裂点位于M-bcr Sca I位点的3'端。对Ph M-bcr断裂点的序列分析未能找到一个能区分异常甲基化和正常甲基化病例的M-bcr核苷酸位置，这表明关键M-bcr序列的易位并非甲基化异常的原因。在8例CML患者中有3例，未携带t(9;22)的细胞被发现具有异常甲基化的未重排M-bcr。数据表明，在Ph断裂点位于M-bcr Sca I位点5'端的CML病例中存在异常甲基化的重排M-bcr，并且CML患者Ph-细胞中的M-bcr也可能异常甲基化。
