title: DNA microarray analysis of natural killer cell-type lymphoproliferative disease of granular lymphocytes with purified CD3-CD56+ fractions.
abstract: Natural killer (NK) cell-type lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the outgrowth of CD3(-)CD16/56(+) NK cells, and can be further subdivided into two distinct categories: aggressive NK cell leukemia (ANKL) and chronic NK lymphocytosis (CNKL). To gain insights into the pathophysiology of NK cell-type LDGL, we here purified CD3(-)CD56(+) fractions from healthy individuals (n=9) and those with CNKL (n=9) or ANKL (n=1), and compared the expression profiles of >12 000 genes. A total of 15 'LDGL-associated genes' were identified, and a correspondence analysis on such genes could clearly indicate that LDGL samples share a 'molecular signature' distinct from that of normal NK cells. With a newly invented class prediction algorithm, 'weighted distance method', all 19 samples received a clinically matched diagnosis, and, furthermore, a detailed cross-validation trial for the prediction of normal or CNKL status could achieve a high accuracy (77.8%). By applying another statistical approach, we could extract other sets of genes, expression of which was specific to either normal or LDGL NK cells. Together with sophisticated statistical methods, gene expression profiling of a background-matched NK cell fraction thus provides us a wealth of information for the LDGL condition.
authors.affiliation: Division of Functional Genomics, Jichi Medical School, Kawachigun, Tochigi, Japan.
authors.forename: Y L
authors.initials: YL
authors.lastname: Choi
authors.forename: H
authors.initials: H
authors.lastname: Makishima
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: R
authors.initials: R
authors.lastname: Ohki
authors.forename: K
authors.initials: K
authors.lastname: Koinuma
authors.forename: J
authors.initials: J
authors.lastname: Ota
authors.forename: Y
authors.initials: Y
authors.lastname: Isobe
authors.forename: F
authors.initials: F
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Oshimi
authors.forename: H
authors.initials: H
authors.lastname: Mano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D002999:Clone Cells; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D012333:RNA, Messenger