MUTATIONAL ANALYSIS OF THE N-RAS GENE IN ACUTE LYMPHOBLASTIC-LEUKEMIA- A STUDY OF 125 JAPANESE PEDIATRIC CASES

A point mutation of the N-ras gene is one of the known genetic alterat ions identified in patients with acute lymphoblastic leukemia (ALL), b ut its clinical importance is still controversial. Using polymerase ch ain reactions, we examined codons 12, 13 and 61 of this gene in 125 Ja panese childhood ALL patients (63 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 r elapsed patients. An N-ras point mutation was observed in 14 (11%) pat ients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, n o correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mu tation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majo rity of the patients (13/14) had an N-ras mutation of a G to A transit ion. This finding was consistent with previous reports on N-ras mutati ons in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies. (C) 1998 El sevier Science Ireland Ltd. All rights reserved.