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.

Methods: The methylation patterns of M-bcr in 23 patients with Ph' positive CML were studied. DNAs extracted from mononuclear cells of both chronic and blastic phases (20 cases) or blastic phases only (3 cases), were doubly digested with restriction enzymes HpaII and BglII, hybridized with a 5'M-bcr probe labeled with 32p-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 patterns were distinct from the chronic patterns as well as the patterns shown in myeloblastic crisis. Moreover, in four out of six patients with lymphoblastic crisis, the chronic patterns were different from those in cases with myeloblastic crisis.

Conclusions: The methylation status of M-bcr was stable during evolution of CML from chronic to myeloblastic phase. Analysis of M-bcr methylation status may be of clinical use in distinguishing lymphoblastic from myeloblastic crisis and predicting the cell lineage of crisis when the disease is still in its chronic phase.