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

CT, clinical trials; LNs, lymph nodes; UTRs, untranslated regions.