PURPOSE: To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL-positive, 16 p210BCR-ABL-positive and 17 BCR-ABL-negative specimens). RESULTS: Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL-positive versus -negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens. This set of 271 differentially expressed genes (including GAB1, CIITA, XBP1, CD83, SERPINB9, PTP4A3, NOV, LOX, CTNND1, BAALC, and RAB21) is enriched for genes involved in cell death, cellular growth and proliferation, and hematologic system development and function. Network analysis demonstrated complex interaction patterns of these genes, and identified FYN and IL15 as the hubs of the top-scoring network. Within the BCR-ABL-positive subgroups, we identified genes overexpressed (PILRB, STS-1, SPRY1) or underexpressed (TSPAN16, ADAMTSL4) in p185BCR-ABL-positive ALL relative to p210BCR-ABL-positive ALL. Finally, we constructed a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1), which correlated with overall survival in BCR-ABL-positive adult ALL (P = .0001), independent of age (P = .25) and WBC count at presentation (P = .003). CONCLUSION: We identified prominent molecular features of BCR-ABL-positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
PURPOSE: To identify gene expression patterns and interaction networks related to BCR-ABL status and clinical outcome in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: DNA microarrays were used to profile a set of 54 adult ALL specimens from the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group E2993 trial (21 p185BCR-ABL-positive, 16 p210BCR-ABL-positive and 17 BCR-ABL-negative specimens). RESULTS: Using supervised and unsupervised analysis tools, we detected significant transcriptomic changes in BCR-ABL-positive versus -negative specimens, and assessed their validity in an independent cohort of 128 adult ALL specimens. This set of 271 differentially expressed genes (including GAB1, CIITA, XBP1, CD83, SERPINB9, PTP4A3, NOV, LOX, CTNND1, BAALC, and RAB21) is enriched for genes involved in cell death, cellular growth and proliferation, and hematologic system development and function. Network analysis demonstrated complex interaction patterns of these genes, and identified FYN and IL15 as the hubs of the top-scoring network. Within the BCR-ABL-positive subgroups, we identified genes overexpressed (PILRB, STS-1, SPRY1) or underexpressed (TSPAN16, ADAMTSL4) in p185BCR-ABL-positive ALL relative to p210BCR-ABL-positive ALL. Finally, we constructed a gene expression- and interaction-based outcome predictor consisting of 27 genes (including GRB2, GAB1, GLI1, IRS1, RUNX2, and SPP1), which correlated with overall survival in BCR-ABL-positive adult ALL (P = .0001), independent of age (P = .25) and WBC count at presentation (P = .003). CONCLUSION: We identified prominent molecular features of BCR-ABL-positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
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: Edwin M Posadas; Hikmat Al-Ahmadie; Victoria L Robinson; Ramasamy Jagadeeswaran; Kristen Otto; Kristen E Kasza; Maria Tretiakov; Javed Siddiqui; Kenneth J Pienta; Walter M Stadler; Carrie Rinker-Schaeffer; Ravi Salgia Journal: BJU Int Date: 2008-10-16 Impact factor: 5.588
Authors: Carolina Vicente-Dueñas; Stefan Janssen; Marina Oldenburg; Franziska Auer; Inés González-Herrero; Ana Casado-García; Marta Isidro-Hernández; Javier Raboso-Gallego; Philipp Westhoff; Aleksandra A Pandyra; Daniel Hein; Katharina L Gössling; Diego Alonso-López; Javier De Las Rivas; Sanil Bhatia; Francisco Javier García-Criado; María Begoña García-Cenador; Andreas P M Weber; Karl Köhrer; Julia Hauer; Ute Fischer; Isidro Sánchez-García; Arndt Borkhardt Journal: Blood Date: 2020-10-29 Impact factor: 22.113