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Two Distinct Gene Expression Signatures in Pediatric Acute Lymphoblastic Leukemia with MLL Rearrangements¹

Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo 153-8904 [S. T., X. G., H. A.]; Department of Pediatrics, Graduate School of Medicine [Ta. T., To. T., Y. H.] and School of Information Science and Technology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655 [K. N.]; Department of Pediatrics, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898 [K. S.]; Department of Pediatrics, Saga Medical School, Saga 849-8501 [E. I.]; Division of Hematology/Oncology, Saitama Children’s Medical Center, Iwatsuki, Saitama 339-8551 [R. H.]; and Cancer Genomics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045 [M. O.], Japan

Acute lymphoblastic leukemia (ALL) with 11q23 translocations is usually associated with MLL gene rearrangement, but little is known about its leukemogenesis. We analyzed the gene expression profiles of pediatric ALL samples according to their translocations. Using oligonucleotide microarray analysis, we identified distinct expression profiles for 23 ALL samples with 11q23 translocations, including t(4;11) (n = 15), t(11;19) (n = 6), and t(5;11) (n = 2), compared with 9 ALL samples with other translocations, including t(12;21) (n = 6) and t(1;19) (n = 3). Gene expression scores of FLT3, MeisI, and CD44 for samples with MLL rearrangements were particularly high compared with those for other ALL samples. Statistical analysis of the gene expression profiles for the 21 ALL samples with MLL rearrangements at diagnosis revealed two subgroups that exclusively correlated with prognosis but not with any other clinico-pathological factor. The transcription factors CBF2 and CDP were highly expressed in the poor and good prognosis subgroups, respectively. In addition, their downstream target genes were differentially expressed. These findings provide new insights into the biological mechanisms of leukemogenesis and prognosis for pediatric ALL with MLL rearrangements.

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