Amplification of AML1 gene is present in childhood acute lymphoblastic leukemia but not in adult, and is not associated with AML1 gene mutation

The AML1/CBFA2/RUNX1 gene is the target of many recurrent translocations seen in different leukemia subtypes. The t(12;21)(p13;q22) is the most frequent translocation observed in childhood B acute lymphoblastic leukemia (ALL), occurring in 20% to 25% of cases. In adult ALL this rearrangement is scarce. Another route of AML1 deregulation could be point mutations in the runt domain. We now report on AML1 amplification in two cases of childhood ALL, found in a series of 107 consecutive children with B-lineage ALL analyzed by fluorescence in situ hybridization (FISH). A parallel analysis of 42 adult B-ALL failed to detect any AML1 rearrangement by FISH. The two patients with AML1 amplification were further analyzed using molecular techniques. SSCP analysis did not detect any mutation. Furthermore, direct sequencing of the cDNA did not reveal any mutation. In conclusion, AML1 amplification seems to be observed only in childhood ALL and is not associated with AML1 gene mutation. Other mechanisms, such as gene dosage effects could be hypothesized.