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

Ash A. Alizadeh, Sean P. Bohen, Chen Lossos, Jose A. Martinez-Climent, Juan Carlos Ramos, Elena Cubedo-Gil, William J. Harrington, Izidore S. Lossos

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Adult T-cell leukemialymphoma (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 AZTIFNα 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 AZTIFNα 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 AZTIFNα therapy may provide novel insights into the mechanisms of action in ATLL.

Original languageEnglish (US)
Pages (from-to)1200-1216
Number of pages17
JournalLeukemia and Lymphoma
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2010

Keywords

  • Chemotherapeutic approaches
  • lymphoid leukemia
  • prognostication
  • transcription factor changes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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