Table 1 TCL1-tg animal models in B-CLL investigation
Function | Mouse model | Findings | Relevance | Ref. |
|---|---|---|---|---|
TCL1 transgenic mouse models | TCL1-tg | TCL1 overexpression is causative for CLL | Mouse without UTRs of human TCL1 | Bichi et al.31 |
TCL1FL-tg | MicroRNAs regulation | Mouse with UTRs of human TCL1 | Efanov et al.32 | |
PI3K/AKT | TCL1-tg cells transplanted into C57bl/6 (i.v.) | AKT targeted therapy (OSU-T315) | Preclinical in vitro and in vivo | Liu et al.37 |
TCL1-tg cells transplanted into B6/C3H (i.p.) | TCL1/AKT/mTOR pathway; mTOR targeted (rapamycin) | CLL pathogenesis; preclinical in vivo | Zanesi et al.38 | |
TCL1-tg cells transplanted into C57bl/6 (i.p.) | Dual PI3K/mTOR inhibitor (PF-04691502) | Preclinical in vitro and in vivo | Blunt et al.39 | |
TCL1-tg | Anti-IGFR1-targeted therapy (linsitinib) | Preclinical in vitro and in vivo; CT | Yaktapour et al.40 | |
TCL1-tg crossed with ROR-Tg | ROR1/TCL1 complex; anti-ROR1 Ab therapy (D10) | Preclinical in vitro and in vivo | Widhopf et al.19 | |
TCL1-tg crossed with Pkc null | PKC/TCL1/AKT route; PCK targeted (enzastaurin) | CLL pathogenesis; CT | Holler et al.41 | |
NFkB | TCL1-tg | IkBα/TCL1 interaction and NFkB activation | Basic research; CLL pathogenesis | Guadio et al.21 |
TCL1-tg cells transplanted into SCID (i.v.) | Anti-HSP90-targeted therapy (17-DMAG alvespimycin) | Preclinical in vivo; CT | Hertlein et al.42 | |
TCL1-tg | XBP1/TCL1 interaction, BCR signaling and IRE1/XBP1 targeted therapy (A-106) | Basic research; CLL pathogenesis; preclinical in vitro and in vivo | Kriss et al.22 | |
TCL1-tg | CLL therapy by ROS induction (Auranofin) | Preclinical in vivo; CT | Fiskus et al.43 | |
Epigenetic regulation | TCL1-tg | TCL1/p50/HDAC1 complex and DNA methylation | Basic research; CLL pathogenesis | Chen et al.23 |
TCL1-tg crossed with Id4+/− | ID4 repression and CLL progression | CLL etiology | Chen et al.44 | |
TCL1-tg | TCL1/DNMT3A-B interaction and DNA methylation | Basic research; CLL pathogenesis | Palamarchuk et al.24 | |
TCL1-tg | DNMT3A-B expression and leukemogenesis | CLL pathogenesis | Chen et al.45 | |
TCL1-tg cells transplanted into SCID (i.v.) | HDAC inhibition (AR-42) | Preclinical in vivo; CT | Lucas et al.47 | |
TCL1-tg crossed with p53 null | p53/miR15-16/Mcl1 axis | CLL pathogenesis | Liu et al.51 | |
TCL1-tg mice | MDM2/p53/miR34a axis | CLL pathogenesis | Asslaber et al.96 | |
TCL1FL-tg cells transplanted into FVB (i.p.) | miR-181b anti-leukemic activity | Preclinical in vitro and in vivo | Bresin et al.58 | |
B-cell receptor | TCL1-tg crossed with dnRag1-Tg | TCL1 enhancement of BCR auto-reactivity | CLL pathogenesis | Nganga et al.65 |
TCL1-tg | TCL1-induced PTPROt inhibition and BCR signal support | CLL pathogenesis | Motiwala et al.66 | |
TCL1-tg crossed with PTPROt-Tg | PTPROt overexpression and CLL phenotype rescue | CLL pathogenesis | Motiwala et al.67 | |
TCL1-tg | BCR resemblance to U-CLLs | CLL pathogenesis | Yan et al.33 | |
TCL1-tg cells serially transferred into SCID | Clonal selection and antigen drive | CLL pathogenesis | Chen et al.69 | |
TCL1-tg | Autonomous BCR signaling | CLL pathogenesis | Duhren-von minden et al.70 | |
TCL1-tg | Intrinsic/extrinsic BCR activation | CLL pathogenesis | Lacovelli et al.71 | |
Inhibitors of BCR signalosome | TCL1-tg | SYK targeted therapy (fostamatinib R788) | CLL pathogenesis; preclinical in vivo; CT | Suljagic et al.72 |
TCL1-tg crossed with XID | Btk inactivation and CLL pathogenesis | CLL pathogenesis | Woyach et al.74 | |
TCL1-tg | BTK targeted therapy (ibrutinib PCI-32765) | Preclinical in vivo; CT | Woyach et al.74 | |
TCL1-tg cells serially transferred into SCID | Ibrutinib mechanism of action | Preclinical in vivo; CT | Ponader et al.76 | |
TCL1-tg crossed with Hs1 null | Hs1 inactivation and CLL progression | CLL pathogenesis | Scielzo et al.78 | |
TCL1-tg cells transplanted into C57bl/6 (i.p.) | Tyrosine kinase inhibitor mechanism of action (dasatinib) | Preclinical in vitro and in vivo; CT | ten Hacken et al.79 | |
Leukemia-environment interplay | TCL1-tg cells serially transferred into SCID | CLL cells proliferation in LNs | CLL pathogenesis | Chen et al.69 |
TCL1-tg | BCR signaling activation in LNs | CLL pathogenesis | Mittal et al.81 | |
TCL1-tg crossed with Cxcr5 null | CXCL13/CXCR5 axis and CLL cells proliferation into LNs | CLL pathogenesis | Heinig et al.82 | |
TCL1-tg | Stroma remodeling by CLL cells; LTβR targeted (LTβR-Ig) | CLL pathogenesis; preclinical in vivo | Heinig et al.82 | |
TCL1-tg crossed with BAFF-Tg | BAFF/NFkB activation and CLL progression | CLL pathogenesis | Enzler et al.83 | |
TCL1-tg crossed with APRIL-Tg | APRIL/TNFR activation and CLL progression | CLL pathogenesis | Lascano et al.84 | |
TCL1-tg crossed with Mif null | MIF and activation of CLL cells and M2 macrophages | CLL pathogenesis | Reinart et al.85 | |
TCL1-tg crossed with Cd44 null | MIF/CD44 interaction and BCR signaling | CLL pathogenesis | Fedorchenko et al.86 | |
TCL1-tg | CD44 antibody-targeting (IM7) | Preclinical in vitro and in vivo | Fedorchenko et al.86 | |
TCL1-tg | IL-10-mediated immunosuppression by CLL cells | CLL pathogenesis | Di Lillo et al.87 | |
TCL1-tg and transplants into young TCL1-tg (i.v.) | T-cells expression profiling and tumor immune response | CLL pathogenesis | Gorgun et al.88 | |
TCL1-tg and TCL1-tg cells transferred into C57bl/6 (i.p.) | T-cells skewing by CLL cells | CLL pathogenesis | Hofbauer et al.89 | |
TCL1-tg | T-cells synapse and immunomodulation (lenalidomide) | CLL pathogenesis; preclinical in vivo; CT | Ramsay et al.90 | |
TCL1-tg and transplants into young TCL1-tg (i.v.) | T-cells defects and PD-1/PD-L1 expression | CLL pathogenesis | McClanahan et al.93 | |
TCL1-tg and TCL1-tg cells transferred into C57bl/6 (i.p.) | T-cells exhaustion and PD-1/PD-L1 blockade | CLL pathogenesis | Gassner et al.92 | |
TCL1-tg cells transplanted into C57bl/6 (i.p.) | T-cell immune response rescue by PD-1/PD-L1 blockade | CLL pathogenesis; preclinical in vivo | McClanahan et al.91 | |
TCL1-tg | Macrophages activation (αCD40 and CpG) | CLL pathogenesis; preclinical in vivo | Wu et al.94 | |
TCL1-tg crossed with Tir8 null | Tir8 inactivation and CLL progression | CLL pathogenesis | Bertilaccio et al.95 |
