MUTATIONS OF THE RAS GENES IN CHILDHOOD ACUTE MYELOID-LEUKEMIA, MYELODYSPLASTIC SYNDROME AND JUVENILE CHRONIC MYELOCYTIC-LEUKEMIA

Using the polymerase chain reaction-single strand conformation polymor phism method and direct sequencing, 12 acute myeloid leukemia (AML) ce ll lines and 108 fresh childhood myeloid tumor specimens, including 67 AML, 29 myelodysplastic syndrome (MDS), and 12 juvenile chronic myelo cytic leukemia (JCML) were examined for mutation in H-, K-, and N-RAS genes. The mutation was found in eight of the 120 samples (6.7%), whic h consisted of four cell lines (33.3%) and four fresh myeloid tumors ( 3.7%). The frequency of the mutation in the cell lines was apparently higher than that in fresh myeloid tumors. K-RAS gene mutations were fo und in two of the 67 fresh AML specimens (3%). Interestingly, these tw o patients had 11q23 translocations. The N-RAS gene mutation was found in one of the 29 specimens (3.4%) of MDS and in one of the 12 specime ns (8.3%) of JCML. All mutations were found in codon 12, 13 or 61 of t he N-RAS and K-RAS genes. Frequency of mutation of RAS genes in fresh myeloid malignancies was very low. These findings suggest that mutatio n of RAS genes does not play an important role in the development of c hildhood myeloid malignancies. (C) 1997 Elsevier Science Ltd.