Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements.
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.
Tsutsumi
Shuichi
S
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan.
Taketani
Takeshi
T
Nishimura
Kunihiro
K
Ge
Xijin
X
Taki
Tomohiko
T
Sugita
Kanji
K
Ishii
Eiichi
E
Hanada
Ryoji
R
Ohki
Misao
M
Aburatani
Hiroyuki
H
Hayashi
Yasuhide
Y
D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D014157:Transcription Factors; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3