Summary of bone marrow transplantation experiments with FOP-FGFR1 and related mutants
Constructs . | Affected/total (no. of expts)* . | Latency, d . | Median survival, d . | RBC, mm3 × 106 . | WBC, mm3 . | Peripheral blood formula, % . | Spleen, cm . | Liver . | Phenotypes at autopsy† . |
|---|---|---|---|---|---|---|---|---|---|
| MSCV | 0/15 (5) | NA | > 365 | 7.1 ± 2.2 | 0.5-2 × 104 | Ly: 84 ± 10 | L: 1.3-1.4 | Normal | Normal |
| Gr: 12.4 ± 7.8 | I: 0.3-0.5 | ||||||||
| M: 3.6 ± 3.3 | |||||||||
| Eo: 0-4 | |||||||||
| FOP-FGFR1 | 12/12 (3) | 32-40‡ | 32 | 6.8 ± 3.2 | 2-8 × 105 | Ly: 9.5 ± 6.8 | L: 2.5-3.0 | Hepatomegaly | MPD |
| Gr: 81.2 ± 7.5 | I: 0.8-1.0 | ||||||||
| M: 3.5 ± 3.2 | |||||||||
| Eo: 0-4 | |||||||||
| Ac: 5.7 ± 2.7 | |||||||||
| FOP-FGFR1 | 0/14 (3) | NA | > 365 | 6.7 ± 3.0 | 0.5-2 × 104 | Ly: 90 ± 6.2 | L: 1.3-1.4 | Normal | Normal |
| K259/A | Gr: 8 ± 5 | I: 0.3-0.5 | |||||||
| M: 2 ± 1.2 | |||||||||
| Eo: 0-3 | |||||||||
| FOP-FGFR1 | 2/17 (3) | 144 | 144 | 6.9 ± 2.3 | 3 × 104-2 × 105 | Variable | L: 2.5-3.5 | Normal | Moderate MPD |
| Y511/F | I: 0.7-1.0 | ||||||||
| 10/17 (3) | 112-322 | 241 | 7.0 ± 0.5 | 2-3 × 104 | Variable | L: 1.2-1.3 | Normal | Moderate MPD | |
| I: 0.3-0.4 | |||||||||
| 5/17 (3) | 91-154 | 119 | 7.1 ± 0.7 | Variable | Variable | L: 1.0-1.3 | Normal | Thymic lymphoma | |
| I: 0.3-0.4 |
Constructs . | Affected/total (no. of expts)* . | Latency, d . | Median survival, d . | RBC, mm3 × 106 . | WBC, mm3 . | Peripheral blood formula, % . | Spleen, cm . | Liver . | Phenotypes at autopsy† . |
|---|---|---|---|---|---|---|---|---|---|
| MSCV | 0/15 (5) | NA | > 365 | 7.1 ± 2.2 | 0.5-2 × 104 | Ly: 84 ± 10 | L: 1.3-1.4 | Normal | Normal |
| Gr: 12.4 ± 7.8 | I: 0.3-0.5 | ||||||||
| M: 3.6 ± 3.3 | |||||||||
| Eo: 0-4 | |||||||||
| FOP-FGFR1 | 12/12 (3) | 32-40‡ | 32 | 6.8 ± 3.2 | 2-8 × 105 | Ly: 9.5 ± 6.8 | L: 2.5-3.0 | Hepatomegaly | MPD |
| Gr: 81.2 ± 7.5 | I: 0.8-1.0 | ||||||||
| M: 3.5 ± 3.2 | |||||||||
| Eo: 0-4 | |||||||||
| Ac: 5.7 ± 2.7 | |||||||||
| FOP-FGFR1 | 0/14 (3) | NA | > 365 | 6.7 ± 3.0 | 0.5-2 × 104 | Ly: 90 ± 6.2 | L: 1.3-1.4 | Normal | Normal |
| K259/A | Gr: 8 ± 5 | I: 0.3-0.5 | |||||||
| M: 2 ± 1.2 | |||||||||
| Eo: 0-3 | |||||||||
| FOP-FGFR1 | 2/17 (3) | 144 | 144 | 6.9 ± 2.3 | 3 × 104-2 × 105 | Variable | L: 2.5-3.5 | Normal | Moderate MPD |
| Y511/F | I: 0.7-1.0 | ||||||||
| 10/17 (3) | 112-322 | 241 | 7.0 ± 0.5 | 2-3 × 104 | Variable | L: 1.2-1.3 | Normal | Moderate MPD | |
| I: 0.3-0.4 | |||||||||
| 5/17 (3) | 91-154 | 119 | 7.1 ± 0.7 | Variable | Variable | L: 1.0-1.3 | Normal | Thymic lymphoma | |
| I: 0.3-0.4 |
RBC indicates erythrocytes; NA indicates not applicable; Ly, lymphocytes; Gr, granulocytes; M, monocytes; Eo, eosinophiles; MPD, myeloproliferative disorder; L, length; I, thickness; Ac, atypical cells.
Number of mice analyzed for each construct × number of independent experiments (expts).
MPD phenotype at biopsy; all mice developed a rapid and fatal MPD characterized by high white blood cell counts (WBCs); inverted peripheral blood formula, splenomegaly, and hepatomegaly; myeloid and megakaryocyte hyperplasia in peripheral blood, spleen, and liver. Cachexia, rear-leg paralysis, and paraspinal hemorrhages were observed. Moderate MPD means that some features described appeared with latency and were reduced as follows: no or moderate elevation of WBC counts. Myeloid hyperplasia in bone marrow was eventually observed as well as cachexia. Enlarged spleens showing slight infiltration with maturing granulocytes and rare megakaryocytes are only observed in 2 of 17 cases; hepatomegaly was never observed. Thymic lymphoma was diagnosed by the presence of a greatly enlarged thymus.
Data obtained from 11 mice; the 12th mouse that was terminally ill was killed 88 days after transplantation.