Lymphomagenesis in HU-NOD/SCID and HU-NSG mice infected with HTLV-1
| CD34+ cell donor tissue ID* . | Mouse strain and age of inoculation† . | Virus‡ . | No. of mice with lymphoma§ . | Percentage of lymphoma‖ . | Avg. time to disease, weeks ± SD . | Avg. time to lymphogenesis, weeks¶ . | Malignant phenotype# . | No. lymphomas serially transplanted** . | Phenotype of transplanted lymphomas†† . |
|---|---|---|---|---|---|---|---|---|---|
| 7698 | NOD/SCID | HTLV-1 | 2/9 | 43.20 | 18.3 ± 2.2 | 16.7 | CD4+CD25− | 2 | CD4+CD25− |
| 15267 | NOD/SCID | HTLV-1 | 2/10 | 18.6 ± 1.01 | CD4+CD25− | 2 | CD4+ CD25− | ||
| 7241 | NOD/SCID | HTLV-1 | 3/5 | 20 ± 3.6 | CD4+CD25low | 3 | CD4+CD25low | ||
| 7749 | NOD/SCID | HTLV-1 | 5/8 | 14 ± 2.2 | CD4+CD25low | 4 | CD4+CD25low | ||
| 7762 | NOD/SCID | HTLV-1 | 4/5 | 16 ± 1.5 | CD4+CD25− | 4 | CD4+CD25− | ||
| 1594 | NSG | HTLV-1 | 4/8 | 62.50 | 14 ± 1.52 | 14.66 | CD4+CD25− | 2 | CD4+CD25− |
| 9321 | NSG | HTLV-1 | 2/3 | 12 ± 3.16 | CD4+CD25− | 1 | CD4+CD25− | ||
| 1735 | NSG | HTLV-1 | 4/5 | 18 ± 2.51 | CD4+CD25− | 3 | CD4+CD25− | ||
| 4399 | NOD/SCID | LV-Tax 1(+) | 0/4 | 26.30 | 0 | 11.7 | NA | ||
| 7749 | NOD/SCID | LV-Tax 1(+) | 2/5 | 8 ± 2.4 | CD4+CD25low | 2 | CD4+CD25low | ||
| 7762 | NOD/SCID | LV-Tax 1(+) | 2/5 | 12 ± 4.2 | CD4+CD25− | 2 | CD4+CD25− | ||
| 15267 | NOD/SCID | Mock | 0/6 | 0 | NA | NA | NA | ||
| 7241 | NOD/SCID | Mock | 0/5 | NA | NA | ||||
| 7749 | NOD/SCID | Mock | 0/8 | NA | NA | ||||
| 7762 | NOD/SCID | Mock | 0/6 | NA | NA | ||||
| 1594 | NSG | Mock | 0/5 | NA | NA | ||||
| 9321 | NSG | Mock | 0/5 | NA | NA |
| CD34+ cell donor tissue ID* . | Mouse strain and age of inoculation† . | Virus‡ . | No. of mice with lymphoma§ . | Percentage of lymphoma‖ . | Avg. time to disease, weeks ± SD . | Avg. time to lymphogenesis, weeks¶ . | Malignant phenotype# . | No. lymphomas serially transplanted** . | Phenotype of transplanted lymphomas†† . |
|---|---|---|---|---|---|---|---|---|---|
| 7698 | NOD/SCID | HTLV-1 | 2/9 | 43.20 | 18.3 ± 2.2 | 16.7 | CD4+CD25− | 2 | CD4+CD25− |
| 15267 | NOD/SCID | HTLV-1 | 2/10 | 18.6 ± 1.01 | CD4+CD25− | 2 | CD4+ CD25− | ||
| 7241 | NOD/SCID | HTLV-1 | 3/5 | 20 ± 3.6 | CD4+CD25low | 3 | CD4+CD25low | ||
| 7749 | NOD/SCID | HTLV-1 | 5/8 | 14 ± 2.2 | CD4+CD25low | 4 | CD4+CD25low | ||
| 7762 | NOD/SCID | HTLV-1 | 4/5 | 16 ± 1.5 | CD4+CD25− | 4 | CD4+CD25− | ||
| 1594 | NSG | HTLV-1 | 4/8 | 62.50 | 14 ± 1.52 | 14.66 | CD4+CD25− | 2 | CD4+CD25− |
| 9321 | NSG | HTLV-1 | 2/3 | 12 ± 3.16 | CD4+CD25− | 1 | CD4+CD25− | ||
| 1735 | NSG | HTLV-1 | 4/5 | 18 ± 2.51 | CD4+CD25− | 3 | CD4+CD25− | ||
| 4399 | NOD/SCID | LV-Tax 1(+) | 0/4 | 26.30 | 0 | 11.7 | NA | ||
| 7749 | NOD/SCID | LV-Tax 1(+) | 2/5 | 8 ± 2.4 | CD4+CD25low | 2 | CD4+CD25low | ||
| 7762 | NOD/SCID | LV-Tax 1(+) | 2/5 | 12 ± 4.2 | CD4+CD25− | 2 | CD4+CD25− | ||
| 15267 | NOD/SCID | Mock | 0/6 | 0 | NA | NA | NA | ||
| 7241 | NOD/SCID | Mock | 0/5 | NA | NA | ||||
| 7749 | NOD/SCID | Mock | 0/8 | NA | NA | ||||
| 7762 | NOD/SCID | Mock | 0/6 | NA | NA | ||||
| 1594 | NSG | Mock | 0/5 | NA | NA | ||||
| 9321 | NSG | Mock | 0/5 | NA | NA |
HTLV-1 indicates human T-lymphotropic virus type-1; HU, humanized; LV, lentiviral vector; NA, not applicable; NOD/SCID, nonobese diabetic severe combined immunodeficiency; NSG, NOD/SCID IL-2γ chainnull.
Mice were inoculated with fresh CD34+ cells derived from human fetal liver.
Three- to 5-week-old NOD/SCID mice or 1- to 2-day-old neonate NSG mice were inoculated with either 5 × 106 (for adults) or 5 × 105 (for neonates) fresh CD34+ cells.
CD34+ HP/HSCs were infected with HTLV-1 or transduced with LVs ex vivo before inoculation into NOD/SCID or NSG mice.
Number of mice that displayed physical signs of leukemia/lymphoma, characterized by hunched posture, lethargy, anemia, and ruffled coat.
Percentage of mice developing lymphoma for each group.
Average time to lymphomagenesis in weeks for each group.
Phenotype of predominant human lymphocytic population in the mesenteric lymph nodes.
Number of lymphomas that engrafted after intraperitoneal injection into naive NOD/SCID recipient mice.
Phenotype displayed by lymphoma cells recovered by peritoneal lavage from secondary recipient mice.