Summary of phenotypes of mice receiving transduced BM cells
| Construct . | No. of evaluable mice . | Disease before d 35 after BMT* . | Disease after d 35 after BMT . | Secondary transplantations† . |
|---|---|---|---|---|
| MigR1 (vector) | 7‡ | None | None (up to 300 d) | Not done |
| P210 | 6‡ | MPD (6/6) Latency: 17-18 d, WBC: 50-420, Spleen wt: 0.3-0.6 g | 100% disease before d 35 | Minority: MPD Majority: T-ALL |
| (1-210) bcr/abl | 15 | MPD (4/15) Latency: 18-28 d, WBC: 46-73, Spleen wt: 0.3-0.5 g B-ALL and MPD (11/15) Latency: 21-27 d, WBC: 30-179, Spleen wt: 0.3-0.6 g | 100% disease before d 35 | 1/4 mice with MPD only used for secondary transplantation, recipients developed B-ALL (latency 60-62 d) 3/11 mice with combined B-ALL and MPD used for secondary transplantation: mouse 7: B-ALL, latency 35 and 37 d mouse 10: 1/3 recipients developed combined MPD, B-ALL, and T-ALL; latency 45 d; 2/3 recipients developed combined B-ALL and T-ALL; latency 45 and 47 d mouse 11: 3/3 recipients developed combined B-ALL and T-ALL; latency 52, 60, and 62 d |
| (1-63) bcr/abl | 13 | None | T-ALL (6/9), latency 97-147 d, WBC 7-37, spleen wt: 0.1-0.3 g, all 6 mice had thymic lymphomas. No evidence of disease in 5 healthy mice killed between d 35 and d 194. One mouse had a pleural effusion at d 165 without evidence of neoplasm. | Not done |
| Δ(1-63) bcr/abl | 10 | None | T-ALL (3/10), latency 155-160 d, WBC 5-19, spleen wt 0.1-0.2 g 1 healthy mouse killed at d 97 without evidence of disease 6 mice are alive and well at 167-260 d after BMT | Not done |
| Tyr177Phe bcr/abl | 12 | None | T-ALL (11/12), latency 73-116 d, WBC 5-67, spleen wt 0.1-0.6, 3/11 mice-thymic lymphoma, 8/11 mice-abdominal lymphoma 1/12 uncertain cause of morbidity (latency 80 d, WBC 17, spleen wt 0.5) | Not done |
| Construct . | No. of evaluable mice . | Disease before d 35 after BMT* . | Disease after d 35 after BMT . | Secondary transplantations† . |
|---|---|---|---|---|
| MigR1 (vector) | 7‡ | None | None (up to 300 d) | Not done |
| P210 | 6‡ | MPD (6/6) Latency: 17-18 d, WBC: 50-420, Spleen wt: 0.3-0.6 g | 100% disease before d 35 | Minority: MPD Majority: T-ALL |
| (1-210) bcr/abl | 15 | MPD (4/15) Latency: 18-28 d, WBC: 46-73, Spleen wt: 0.3-0.5 g B-ALL and MPD (11/15) Latency: 21-27 d, WBC: 30-179, Spleen wt: 0.3-0.6 g | 100% disease before d 35 | 1/4 mice with MPD only used for secondary transplantation, recipients developed B-ALL (latency 60-62 d) 3/11 mice with combined B-ALL and MPD used for secondary transplantation: mouse 7: B-ALL, latency 35 and 37 d mouse 10: 1/3 recipients developed combined MPD, B-ALL, and T-ALL; latency 45 d; 2/3 recipients developed combined B-ALL and T-ALL; latency 45 and 47 d mouse 11: 3/3 recipients developed combined B-ALL and T-ALL; latency 52, 60, and 62 d |
| (1-63) bcr/abl | 13 | None | T-ALL (6/9), latency 97-147 d, WBC 7-37, spleen wt: 0.1-0.3 g, all 6 mice had thymic lymphomas. No evidence of disease in 5 healthy mice killed between d 35 and d 194. One mouse had a pleural effusion at d 165 without evidence of neoplasm. | Not done |
| Δ(1-63) bcr/abl | 10 | None | T-ALL (3/10), latency 155-160 d, WBC 5-19, spleen wt 0.1-0.2 g 1 healthy mouse killed at d 97 without evidence of disease 6 mice are alive and well at 167-260 d after BMT | Not done |
| Tyr177Phe bcr/abl | 12 | None | T-ALL (11/12), latency 73-116 d, WBC 5-67, spleen wt 0.1-0.6, 3/11 mice-thymic lymphoma, 8/11 mice-abdominal lymphoma 1/12 uncertain cause of morbidity (latency 80 d, WBC 17, spleen wt 0.5) | Not done |
The characteristics of the MPD are discussed in the text and by Pear et al.17 The MPD is characterized by increased WBC counts, composed primarily of mature granulocytes, hepatosplenomegaly with extensive extramedullary hematopoiesis, and tissue invasion by mature myeloid cells. All mice also developed pulmonary hemorrhage due to infiltrating myeloid cells. The B-ALL and T-ALL are described in the text. WBC count is per 106cells/mL.
1 × 106 spleen cells from primary mice were injected intravenously into each sublethally irradiated (450 R) syngeneic recipient.
We have previously analyzed 10 additional MigR1 and P210 mice with identical findings.17