Expression profiles of adult T-cell leukemia-lymphoma and associations with clinical responses to zidovudine and interferon α

• Published in: Leukemia & lymphoma 2010-07, Vol.51 (7), p.1200-1216
• Main Authors: Alizadeh, Ash A., Bohen, Sean P., Lossos, Chen, Martinez-Climent, Jose A., Ramos, Juan Carlos, Cubedo-Gil, Elena, Harrington, William J., Lossos, Izidore S.
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Chemotherapeutic approaches; Comparative Genomic Hybridization; Drug Therapy, Combination; Gene Expression Profiling; Humans; Interferon-alpha - therapeutic use; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemia-Lymphoma, Adult T-Cell - pathology; lymphoid leukemia; Oligonucleotide Array Sequence Analysis; prognostication; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; transcription factor changes; Treatment Outcome; Zidovudine - therapeutic use
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428191003728628

Adult T-cell leukemia-lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from nine patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon α (IFNα). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2, and LMO2, and confirmed LMO2 expression in ATLL cells at the protein level. In vivo AZT-IFNα therapy evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycle regulated genes, including those encoding ribosomal proteins. Remarkably, patients not responding to AZT-IFNα differed most from responding patients in lower expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT-IFNα therapy may provide novel insights into the mechanisms of action in ATLL.