Adult T-cell leukemia-lymphoma and AZT-IFNa combination therapy

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 9 patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon alpha (IFN). 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, with confirmation of LMO2 expression confirmed in ATLL cells at the protein level. In vivo AZT- and IFNa treatment evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycles regulated genes including those encoding ribosomal proteins. Remarkably, patients not responding to IFNa/AZT differed most from responding patients in relative over 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-IFNa therapy may provide novel insights into the mechanisms of action in ATLL. compound_treatment_design