Table 3.
Preclinical murine BCP-ALL infection models
| Primary oncogenic lesion | Treatment | Outcome | Comment | References |
|---|---|---|---|---|
| Transgenic, retroviral LTR-driven ETV6-RUNX1 expression | No treatment | Decreased B-cell differentiation of early B-cell progenitors (Cd19− to pro-B) to pre-B cells | First model of ETV6-RUNX1 preleukemia | 162 |
| Transgenic, β-globin promoter–driven ETV6-RUNX1 expression, lymphoid lineage specificity via IGH chain enhancer | No treatment | Expansion of early B-cell progenitors (Cd34+Cd38−Cd19+) | First lymphoid lineage-specific model of ETV6-RUNX1 preleukemia | 26 |
| Heterozygous knockout, Pax5+/− | Exposure to infectious environment | BCP-ALL, ∼22% of mice | First in vivo model recapitulating human Pax5+/− BCP-ALL | 31 |
| Transgenic, retroviral LTR-driven ETV6-RUNX1 expression | NOD-SCID transplanted with pretreated Aicda+/+Rag1+/+ETV6-RUNX1 cells (IL-7 withdrawal, LPS treatment of AID activation) | 100% BCP-ALL in ex vivo LPS-treated Aicda+/+Rag1+/+ background | First murine model showing the impact of bacterial infection on ETV6-RUNX1+ leukemia development | 24 |
| Transgenic, Eμ-promoter-driven Ret expression | Treatment of IFNγ+/+ Eμ-ret mice with TLR ligands | Delay of BCP- ALL | First model of leukemia prevention through targeting IFN pathways | 29 |
| Transgenic, conditional E2A-promoter-driven E2A-PBX1 expression induced by Cd19-, Mb1-, or Mx1-driven Cre expression | No treatment | BCP-ALL: 7% Cd19-Cre line, 53% Mb1-Cre line, 59% Mx1-Cre line | First in vivo model recapitulating human E2A-PBX1 BCP-ALL | 163 |
| Transgenic, conditional E2A-promoter-driven E2A-PBX1 expression induced by Cd19-, Mb1-, or Mx1-driven Cre expression; Pax5+/− | No treatment | Heterozygous deletion of Pax5 substantially increased penetrance and shortened BCP-ALL latency | Confirmed a tumor-suppressive role for Pax5 in the TgE2A-PBX1 background | 163 |
| Transgenic, Sca1-promoter-driven ETV6-RUNX1 expression | Exposure to infectious environment | BCP-ALL, ∼10% of mice | First in vivo model recapitulating human ETV6-RUNX1+ BCP-ALL | 30 |
| Heterozygous knock-out, Pax5+/− Aid+/− | Exposure to infectious environment | BCP-ALL, ∼30% of mice | First model showing that AID does not affect latency or incidence of infection-mediated Pax5+/− BCP-ALL development | 32 |
| Hetero- and homozygous knock-out, Pax5+/− Aid−/− | Exposure to infectious environment | BCP-ALL, ∼30% of mice | ||
| Heterozygous knockout of Pax5+/− in heterozygous ν+ mice | Exposure to infectious environment | BCP-ALL, ∼15% of mice | First model showing that the infection-driven BCP-ALL development in Pax5+/− mice is not dependent on T cells | 81 |
| Heterozygous knockout Pax5+/− in homozygous ν/ν mice | Exposure to infectious environment | BCP-ALL, ∼15% of mice |
LPS, lipopolysaccharide.