Supplementary Data. 1. Supplementary Methods 2. Supplementary Data Supplementary Table 1, Patient information at sampling. Supplementary Figure 1, A: Genomic alterations of both tumor and normal samples in Cases A-16, A-20, and A-35. B: Analysis of TCR-γ gene rearrangement in a case. Supplementary Figure 2, Re-expression of INK4a or ARF into ATL cell lines. Supplementary Table 2, Status of CD58 and B2M in ATL samples. Supplementary Table 3, Genetic alterations related to acute transformation of chronic type ATL. 3. References
ARTICLE ABSTRACT
Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1–induced neoplasm with four clinical subtypes: acute, lymphoma, chronic, and smoldering. Although the chronic type is regarded as indolent ATL, about half of the cases progress to acute-type ATL. The molecular pathogenesis of acute transformation in chronic-type ATL is only partially understood. In an effort to determine the molecular pathogeneses of ATL, and especially the molecular mechanism of acute transformation, oligo-array comparative genomic hybridization and comprehensive gene expression profiling were applied to 27 and 35 cases of chronic and acute type ATL, respectively. The genomic profile of the chronic type was nearly identical to that of acute-type ATL, although more genomic alterations characteristic of acute-type ATL were observed. Among the genomic alterations frequently observed in acute-type ATL, the loss of CDKN2A, which is involved in cell-cycle deregulation, was especially characteristic of acute-type ATL compared with chronic-type ATL. Furthermore, we found that genomic alteration of CD58, which is implicated in escape from the immunosurveillance mechanism, is more frequently observed in acute-type ATL than in the chronic-type. Interestingly, the chronic-type cases with cell-cycle deregulation and disruption of immunosurveillance mechanism were associated with earlier progression to acute-type ATL. These findings suggested that cell-cycle deregulation and the immune escape mechanism play important roles in acute transformation of the chronic type and indicated that these alterations are good predictive markers for chronic-type ATL. Cancer Res; 74(21); 6129–38. ©2014 AACR.
