Involvement of the MLL/ALL-1 gene associated with multiple point mutations of the N-ras gene in acute myeloid leukemia with t(11;17)(q23;q25)

To the Editor: tion. She received combination chemotherapy and achieved complete remission. However, 1.5 years later, the AML relapsed despite the intermittent intensification, and she died of cerebral bleeding. Karyotype analysis of the blast cells at diagnosis showed 46 XX with the t( I I ; I 7)(q23;q25) translocation in 20 of 20 analyzed cells. The breakpoints of the MLL/ALL-I gene have been clustered within the BumHI 9-kb genomic fragment, which can be detected by the BumHl0.9-kbcDNA fragment’”(Fig 1). Southern blotanalysis using this probe showed two rearranged bands in the BamHI digested DNA, and one rearranged band accompanied with a relatively fainter germ line band at 5.5 kb in the EcoRV digested DNA (Fig I) , which suggested that the MLL/ALL-1 gene was disrupted within the EcoRV-BamHI 5-kb fragment and jointed presumably with a DNA fragment on 37q25. Furthermore, the blast cells at diagnosis had the multiple-point mutations of the N-rus gene.’ cDNA ofthe N-rasgene were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and were cloned into the M I3mpl8 vector. The presence of mutations in 90 clones was analyzed by means of oligonucleotide hybridization (Table l). Two clones containing double-loci mutations at codons 13 and 61 were detected in the same allele. Forty clonescontained each mutation at codons 12, 13, and 6 I . and the remaining 48 clones showed the wild-type of N-ras gene. Southern blot analysis of the N-ras gene Chromosome I 1 band q23 ( I lq23) is one of the most frequent disrupting regions of the chromosome translocations and deletions in various types ofleukemia, lymphomas, and myelodysplastic syndromes.’ The partner regions for the reciprocal translocations are lp32, lq21, 2p21, 4q21, 6q27, 9p22, IOp15, 14q32, 17q25, and 19~13.’ Recent studies have shown that the MLL/ALL-1 gene is involved in the t(4;l l)(q21;q23) and t(l1;19)(q23:p13) translocations of infantile acute leukemia with biphenotypic character.3-’ Furthermore, this gene also associated with t( l ; I I ) , t(6;l I ) and t(9; I 1): The MLL/ALL-I gene encodes for a human homologue of the Drosophila trithorax protein that fuses to the partner chromosome-encoded protein, producing a fusion transcriptional fact ~ r . ’ . ~ . ~ Thus, the MLL/ALL-I gene is likely to be associated with leukemogenesis in the 1 lq23 translocation. We present here a case ofacute myeloidleukemia(AML) with the t( 11;17)(q23;q25) translocation showing the rearrangement ofthe MLL/ALL-I gene associated with multiple N-ras gene mutations. A 9-year-old girl was refereed to us for AML (MI) according to the French-American-British (FAB) classification, with a leukocyte count of85 X IO’lpL, hemoglobin (Hb) 8. I g/dL, and platelets 30 X IO’lpL. She had been healthy except some episodes of viral infec-