PURPOSE: To characterize gene expression signatures in acute lymphocytic leukemia (ALL) cells associated with known genotypic abnormalities in adult patients. EXPERIMENTAL DESIGN: Gene expression profiles from 128 adult patients with newly diagnosed ALL were characterized using high-density oligonucleotide microarrays. All patients were enrolled in the Italian GIMEMA multicenter clinical trial 0496 and samples had >90% leukemic cells. Uniform phenotypic, cytogenetic, and molecular data were also available for all cases. RESULTS: T-lineage ALL was characterized by a homogeneous gene expression pattern, whereas several subgroups of B-lineage ALL were evident. Within B-lineage ALL, distinct signatures were associated with ALL1/AF4 and E2A/PBX1 gene rearrangements. Expression profiles associated with ALL1/AF4 and E2A/PBX1 are similar in adults and children. BCR/ABL+ gene expression pattern was more heterogeneous and was most similar to ALL without known molecular rearrangements. We also identified a set of 83 genes that were highly expressed in leukemia blasts from patients without known molecular abnormalities who subsequently relapsed following therapy. Supervised analysis of kinase genes revealed a high-level FLT3 expression in a subset of cases without molecular rearrangements. Two other kinases (PRKCB1 and DDR1) were highly expressed in cases without molecular rearrangements, as well as in BCR/ABL-positive ALL. CONCLUSIONS: Genomic signatures are associated with phenotypically and molecularly well defined subgroups of adult ALL. Genomic profiling also identifies genes associated with poor outcome in cases without molecular aberrations and specific genes that may be new therapeutic targets in adult ALL.
PURPOSE: To characterize gene expression signatures in acute lymphocytic leukemia (ALL) cells associated with known genotypic abnormalities in adult patients. EXPERIMENTAL DESIGN: Gene expression profiles from 128 adult patients with newly diagnosed ALL were characterized using high-density oligonucleotide microarrays. All patients were enrolled in the Italian GIMEMA multicenter clinical trial 0496 and samples had >90% leukemic cells. Uniform phenotypic, cytogenetic, and molecular data were also available for all cases. RESULTS: T-lineage ALL was characterized by a homogeneous gene expression pattern, whereas several subgroups of B-lineage ALL were evident. Within B-lineage ALL, distinct signatures were associated with ALL1/AF4 and E2A/PBX1 gene rearrangements. Expression profiles associated with ALL1/AF4 and E2A/PBX1 are similar in adults and children. BCR/ABL+ gene expression pattern was more heterogeneous and was most similar to ALL without known molecular rearrangements. We also identified a set of 83 genes that were highly expressed in leukemia blasts from patients without known molecular abnormalities who subsequently relapsed following therapy. Supervised analysis of kinase genes revealed a high-level FLT3 expression in a subset of cases without molecular rearrangements. Two other kinases (PRKCB1 and DDR1) were highly expressed in cases without molecular rearrangements, as well as in BCR/ABL-positive ALL. CONCLUSIONS: Genomic signatures are associated with phenotypically and molecularly well defined subgroups of adult ALL. Genomic profiling also identifies genes associated with poor outcome in cases without molecular aberrations and specific genes that may be new therapeutic targets in adult ALL.
Authors: Zejuan Li; Roger T Luo; Shuangli Mi; Miao Sun; Ping Chen; Jingyue Bao; Mary Beth Neilly; Nimanthi Jayathilaka; Deborah S Johnson; Lili Wang; Catherine Lavau; Yanming Zhang; Charles Tseng; Xiuqing Zhang; Jian Wang; Jun Yu; Huanming Yang; San Ming Wang; Janet D Rowley; Jianjun Chen; Michael J Thirman Journal: Cancer Res Date: 2009-01-20 Impact factor: 12.701
Authors: Olga Sala-Torra; Holly M Gundacker; Derek L Stirewalt; Paula A Ladne; Era L Pogosova-Agadjanyan; Marilyn L Slovak; Cheryl L Willman; Shelly Heimfeld; David H Boldt; Jerald P Radich Journal: Blood Date: 2007-04-01 Impact factor: 22.113
Authors: Akinori Yoda; Yuka Yoda; Sabina Chiaretti; Michal Bar-Natan; Kartik Mani; Scott J Rodig; Nathan West; Yun Xiao; Jennifer R Brown; Constantine Mitsiades; Martin Sattler; Jeffrey L Kutok; Daniel J DeAngelo; Martha Wadleigh; Alfonso Piciocchi; Paola Dal Cin; James E Bradner; James D Griffin; Kenneth C Anderson; Richard M Stone; Jerome Ritz; Robin Foà; Jon C Aster; David A Frank; David M Weinstock Journal: Proc Natl Acad Sci U S A Date: 2009-12-15 Impact factor: 11.205
Authors: Sabina Chiaretti; Antonella Vitale; Gianni Cazzaniga; Sonia Maria Orlando; Daniela Silvestri; Paola Fazi; Maria Grazia Valsecchi; Loredana Elia; Anna Maria Testi; Francesca Mancini; Valentino Conter; Geertruy te Kronnie; Felicetto Ferrara; Francesco Di Raimondo; Alessandra Tedeschi; Giuseppe Fioritoni; Francesco Fabbiano; Giovanna Meloni; Giorgina Specchia; Giovanni Pizzolo; Franco Mandelli; Anna Guarini; Giuseppe Basso; Andrea Biondi; Robin Foà Journal: Haematologica Date: 2013-05-28 Impact factor: 9.941