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Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). In addition to HTLV-1 bZIP factor (HBZ), a leukemogenic antisense transcript of HTLV-1, abnormalities of genes involved in TCR-NF-κB signaling such as CARD11 have been detected in about 90% of patients. Utilizing mouse models with T cell-specific CARD11(E626K) expression and/or CD4+ T cell-specific HBZ expression, namely CARD11(E626K)CD4-Cre mice, HBZ transgenic (Tg) mice, and CARD11(E626K)CD4-Cre;HBZ Tg compound mice, we clarified the effect of these genes on pathogenesis. Both CARD11(E626K)CD4-Cre and HBZ Tg mice developed lymphoproliferative disease, and the compound mice showed accelerated disease and increased CD4+ T cells in vivo. CARD11(E626K) and HBZ cooperatively activated the NF-κB non-canonical pathway, IRF4 targets, and cell proliferation. Most of the KEGG and HALLMARK gene sets, which are enriched in acute-type ATL, were also enriched in the compound mice, indicating that these genes cooperatively form the pathological basis for ATL development.

Background The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.