| First Author | Kameda T | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 1309 |
| PubMed ID | 36446869 | Mgi Jnum | J:331703 |
| Mgi Id | MGI:7397357 | Doi | 10.1038/s42003-022-04284-x |
| Citation | Kameda T, et al. (2022) CARD11 mutation and HBZ expression induce lymphoproliferative disease and adult T-cell leukemia/lymphoma. Commun Biol 5(1):1309 |
| abstractText | 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-kappaB signaling, such as CARD11, are detected in about 90% of patients. Utilizing mice expressing CD4(+) T cell-specific CARD11(E626K) and/or CD4(+) T cell-specific HBZ, namely CARD11(E626K)(CD4-Cre) mice, HBZ transgenic (Tg) mice, and CARD11(E626K)(CD4-Cre);HBZ Tg double transgenic mice, we clarify these genes' pathogenetic effects. CARD11(E626K)(CD4-Cre) and HBZ Tg mice exhibit lymphocytic invasion to many organs, including the lungs, and double transgenic mice develop lymphoproliferative disease and increase CD4(+) T cells in vivo. CARD11(E626K) and HBZ cooperatively activate the non-canonical NF-kappaB pathway, IRF4 targets, BATF3/IRF4/HBZ transcriptional network, MYC targets, and E2F targets. Most KEGG and HALLMARK gene sets enriched in acute-type ATL are also enriched in double transgenic mice, indicating that these genes cooperatively contribute to ATL development. |
