Characteristics of recipients of p210 BCR/ABLwild-type-transduced and Y177F-transduced bone marrow
| Mouse . | Latency* . | Diagnosis† . | PB WBC/ differential‡ . | Spleen Wt (g) . | Clinicopathologic features1-153 . | Clonality by Southern blot 1-155 . |
|---|---|---|---|---|---|---|
| p210 wild-type recipients1-154 | ||||||
| n = 15# | 21 ± 2 | CML | 323 000 ± 75 000 80% neutrophils | 1.1 ± 0.3 | Hepatosplenomegaly, normal LN, thymus | 9 ± 4 proviral clones common to neutrophils, ma, erythroid, and B-lymphoid cells |
| p210 Y177F recipients | ||||||
| 1 | 72 | B-ALL | ND | 0.48 | Enlarged inguinal LN, normal thymus, hindlimb paralysis | Monoclonal (spleen) |
| 2 | 80 | B-ALL | ND | 0.17 | Bloody pleural effusion (B220+), normal LN, thymus | Biclonal (LN) |
| 3 | 95 | B-ALL + T-ALL (+CML) | 101 000 80% neutrophils | 0.29 | Enlarged LN and thymus, bloody pleural effusion | Biclonal (spleen) 4 clones (pleural effusion) with 2 TCRβ rearrangements 1 unique clone (PB neutrophils) |
| 4 | 105 | T-ALL | 3200 50% neutrophils 20% lymphoblasts | 0.22 | Abdominal tumor with ascites (CD24+, B220−), bloody pleural effusion, enlarged thymus | Monoclonal (tumor, thymus), with clonal biallelic TCRβ gene rearrangements1-160 |
| 5 | 105 | T-ALL | 4700 50% lymphoblasts | 0.15 | Abdominal tumor, bloody pleural effusion, enlarged thymus | Biclonal (spleen), monoclonal (tumor) with clonal biallelic TCRβ rearrangement |
| 6 | 107 | T-ALL | 7400 50% lymphoblasts | 0.07 | Bloody pleural effusion, large thymic mass (Thy-1+, CD8+, B220−) | Biclonal (thymic mass) with 4 TCRβ gene rearrangements1-160 |
| 7 | 109 | T-ALL (+CML) | 356 000 80% neutrophils | 0.46 | Abdominal tumor with ascites, slightly enlarged thymus, splenic neutrophil infiltration | Monoclonal (tumor, thymus), 1 unique clone (PB neutrophils)1-164 |
| 8 | 113 | T-ALL (+CML) | 48 000 70% neutrophils 30% lymphoblasts | 0.20 | Abdominal tumor with ascites (Thy-1+, CD4/8+, B220−), enlarged thymus, pleural effusion | Monoclonal (tumor, thymus), 1 unique clone (PB neutrophils)1-164 |
| 9 | 113 | T-ALL | 10 800 70% neutrophils 20% sm. lymphoid | 0.13 | Abdominal tumor (Thy-1+, CD8+, B220−), bloody pleural effusion, enlarged thymus, paraspinous mass | 3 clones (tumor, thymus) |
| 10 | 155 | T-ALL (+CML) | 73 000 80% neutrophils | 0.18 | Abdominal tumor, pleural effusion (ma) | 4 clones (tumor) |
| Mouse . | Latency* . | Diagnosis† . | PB WBC/ differential‡ . | Spleen Wt (g) . | Clinicopathologic features1-153 . | Clonality by Southern blot 1-155 . |
|---|---|---|---|---|---|---|
| p210 wild-type recipients1-154 | ||||||
| n = 15# | 21 ± 2 | CML | 323 000 ± 75 000 80% neutrophils | 1.1 ± 0.3 | Hepatosplenomegaly, normal LN, thymus | 9 ± 4 proviral clones common to neutrophils, ma, erythroid, and B-lymphoid cells |
| p210 Y177F recipients | ||||||
| 1 | 72 | B-ALL | ND | 0.48 | Enlarged inguinal LN, normal thymus, hindlimb paralysis | Monoclonal (spleen) |
| 2 | 80 | B-ALL | ND | 0.17 | Bloody pleural effusion (B220+), normal LN, thymus | Biclonal (LN) |
| 3 | 95 | B-ALL + T-ALL (+CML) | 101 000 80% neutrophils | 0.29 | Enlarged LN and thymus, bloody pleural effusion | Biclonal (spleen) 4 clones (pleural effusion) with 2 TCRβ rearrangements 1 unique clone (PB neutrophils) |
| 4 | 105 | T-ALL | 3200 50% neutrophils 20% lymphoblasts | 0.22 | Abdominal tumor with ascites (CD24+, B220−), bloody pleural effusion, enlarged thymus | Monoclonal (tumor, thymus), with clonal biallelic TCRβ gene rearrangements1-160 |
| 5 | 105 | T-ALL | 4700 50% lymphoblasts | 0.15 | Abdominal tumor, bloody pleural effusion, enlarged thymus | Biclonal (spleen), monoclonal (tumor) with clonal biallelic TCRβ rearrangement |
| 6 | 107 | T-ALL | 7400 50% lymphoblasts | 0.07 | Bloody pleural effusion, large thymic mass (Thy-1+, CD8+, B220−) | Biclonal (thymic mass) with 4 TCRβ gene rearrangements1-160 |
| 7 | 109 | T-ALL (+CML) | 356 000 80% neutrophils | 0.46 | Abdominal tumor with ascites, slightly enlarged thymus, splenic neutrophil infiltration | Monoclonal (tumor, thymus), 1 unique clone (PB neutrophils)1-164 |
| 8 | 113 | T-ALL (+CML) | 48 000 70% neutrophils 30% lymphoblasts | 0.20 | Abdominal tumor with ascites (Thy-1+, CD4/8+, B220−), enlarged thymus, pleural effusion | Monoclonal (tumor, thymus), 1 unique clone (PB neutrophils)1-164 |
| 9 | 113 | T-ALL | 10 800 70% neutrophils 20% sm. lymphoid | 0.13 | Abdominal tumor (Thy-1+, CD8+, B220−), bloody pleural effusion, enlarged thymus, paraspinous mass | 3 clones (tumor, thymus) |
| 10 | 155 | T-ALL (+CML) | 73 000 80% neutrophils | 0.18 | Abdominal tumor, pleural effusion (ma) | 4 clones (tumor) |
Time in days to premorbidity or death after transplantation of transduced bone marrow.
Diagnosis based on histopathology, immunophenotype, and molecular analysis as discussed in the text: B-ALL, B-lymphoid leukemia; T-ALL, T-lymphoid leukemia; (+CML), indicates mouse with excess circulating neutrophils (see text).
Peripheral blood leukocyte count (per μL) and differential; ND, not determined.
Based on gross and microscopic pathology and flow cytometric analysis; LN, lymph node; ma, macrophage.
Analysis of proviral integration pattern by Southern blot.
Average ± standard error; data from reference 14.
#Four additional recipients of p210 WT-transduced marrow were analyzed in addition to mice previously reported (reference 14).
See Figure 3C.
See Figure 4A.