title: Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARalpha).
abstract: Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15;17)(q22;q12) [French-American-British or FAB-M3 with t(15;17)] and AML without maturation (FAB-M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate sigma-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15;17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15;17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15;17). Growth factor-binding protein 2 gene was down-regulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor beta, folate receptor beta, low affinity immunoglobulin gamma, Fc receptor IIC precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15;17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality t(15;17)(q22;q12).
authors.affiliation: The Second Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Morikawa
authors.forename: Huai
authors.initials: H
authors.lastname: Li
authors.forename: Seungchan
authors.initials: S
authors.lastname: Kim
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
authors.forename: Edward
authors.initials: E
authors.lastname: Suh
authors.forename: Edward
authors.initials: E
authors.lastname: Dougherty
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Tohru
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000465:Algorithms; D002454:Cell Differentiation; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D000071156:Promyelocytic Leukemia Protein; D012313:RNA / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
chemical_list: D018076:DNA, Complementary; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D012313:RNA