DIFFERENT METHYLATION PATTERNS OF THE M-BCR GENE IN MYELOBLASTIC AND LYMPHOBLASTIC CRISIS OF CHRONIC MYELOCYTIC-LEUKEMIA

Objective. To investigate the relationship between methylation status of M-bcr gene and transformation of chronic myelocytic leukemia (CML) from chronic to blastic phase. Material and Methods. The methylation p atterns of M-bcr in 23 patients with Ph' positive CML were studied. DN As extracted from mononuclear cells of both chronic and blastic phases (20 cases) or blastic phases only (3 cases), were doubly digested wit h restriction enzymes HpaII and BglII, hybridized with a 5'M-bcr probe labeled with (32)p-deoxycytidine triphosphate, and autoradiographed. Results. In all the patients with myeloblastic crisis, DNAs from both chronic and blastic cells of each patient showed identical methylation patterns. There was substantial heterogeneity in methylation patterns in the patients with lymphoblastic crisis. All the lymphoblastic patt erns were distinct from the chronic patterns as well as the patterns s hown in myeloblastic crisis. Moreover, in four out of six patients wit h lymphoblastic crisis, the chronic patterns were different from those in cases with myeloblastic crisis. Conclusions. The methylation statu s of M-bcr was stable during evolution of CML from chronic to myelobla stic phase. Analysis of M-bcr methylation status may be of clinical us e in distinguishing lymphoblastic from myeloblastic crisis and predict ing the cell lineage of crisis when the disease is still in its chroni c phase.