biostudies-literatureKameda TMEXT | Japan Society for the Promotion of ScienceJapan Agency for Medical Research and Development1309https://www.ebi.ac.uk/biostudies/studies/S-EPMC9709164biostudies-literatureUnknown5(1)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, 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⁺ Communications biologyCARD11 mutation and HBZ expression induce lymphoproliferative disease and adult T-cell leukemia/lymphoma.PMC970916417K0993120ck0106538h000120ck0106409h0003Kamiunten ATahira YMatsuda TKoya JKitai YKataoka KYokomizo-Nakano TKubota SKogure YKameda TSugiyama MShide KMarutsuka KOhshima TMorishita DSashida GHidaka TKubuki YOgawa SSekine MAkizuki KShimoda KYoda AfalseCARD11 mutation and HBZ expression induce lymphoproliferative disease and adult T-cell leukemia/lymphoma.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, 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⁺ 2022-01-01T00:00:00Z2022 Nov2025-04-03T21:31:04.684Z2025-04-03T21:31:04.684ZS-EPMC97091643644686910.1038/s42003-022-04284-x