Table 1.

Clinical characteristics of induced human SCLtTA/BCR-ABL double-transgenic animals at time of death


Animal

Clinical condition

WBC/μL, neutrophils (%)*

Hgb (g/dL)

Spleen weight, mg

Other organs involved, gross pathology/histology

Time of analysis, d
W98   Moribund   25 800 (33)   10.5   410  LN, skin, lung bleed, PB lymphoblasts   29  
W107   Moribund, tumor right cervival LN   8 300 (32)   12.5   240   Axillary LN (923 mg), liver, lung bleed   122  
W109   Moribund   3 900 (26)   ND   310   Liver, LN, lung bleed   105  
W110   Moribund   29 200 (82)   8.2   850   Kidney, perinephric fluid, liver, skin, LN (all myeloid cells), brittle bones   57  
W114   Moribund   18 500 (61)   12   240  LN, liver (myeloid cells), lung bleed, brittle bones   46  
W118   Leukocytosis   15 500 (51)   14   260   Liver, pale BM   43  
W119   Leukocytosis, anemia   70 000 (27)   10.5   480   LN, liver, pale BM, PB lymphoblasts (70%)   34  
W184   Moribund   > 30 000 (34)   ND   130   LN (mild), brittle bones   67  
W185   Neutrophilia, humanely killed   9 200 (54)   ND   300   Pale BM   42  
W194   Found dead   25 300 (ND)   ND   440   Kidney, liver   66  
W202   Neutrophilia, humanely killed   9 500 (50)   ND   270   pale BM   30  
W207   Moribund, distended abdomen   22 000 (53)   ND   400   Liver, kidney   69  
W209   Moribund   19 600 (63)   ND   130   LN (mild)   42  
W214
 
Humanely killed
 
6 800 (26)
 
ND
 
120
 
None
 
7
 

Animal

Clinical condition

WBC/μL, neutrophils (%)*

Hgb (g/dL)

Spleen weight, mg

Other organs involved, gross pathology/histology

Time of analysis, d
W98   Moribund   25 800 (33)   10.5   410  LN, skin, lung bleed, PB lymphoblasts   29  
W107   Moribund, tumor right cervival LN   8 300 (32)   12.5   240   Axillary LN (923 mg), liver, lung bleed   122  
W109   Moribund   3 900 (26)   ND   310   Liver, LN, lung bleed   105  
W110   Moribund   29 200 (82)   8.2   850   Kidney, perinephric fluid, liver, skin, LN (all myeloid cells), brittle bones   57  
W114   Moribund   18 500 (61)   12   240  LN, liver (myeloid cells), lung bleed, brittle bones   46  
W118   Leukocytosis   15 500 (51)   14   260   Liver, pale BM   43  
W119   Leukocytosis, anemia   70 000 (27)   10.5   480   LN, liver, pale BM, PB lymphoblasts (70%)   34  
W184   Moribund   > 30 000 (34)   ND   130   LN (mild), brittle bones   67  
W185   Neutrophilia, humanely killed   9 200 (54)   ND   300   Pale BM   42  
W194   Found dead   25 300 (ND)   ND   440   Kidney, liver   66  
W202   Neutrophilia, humanely killed   9 500 (50)   ND   270   pale BM   30  
W207   Moribund, distended abdomen   22 000 (53)   ND   400   Liver, kidney   69  
W209   Moribund   19 600 (63)   ND   130   LN (mild)   42  
W214
 
Humanely killed
 
6 800 (26)
 
ND
 
120
 
None
 
7
 

Clinical condition refers to the condition of the animals at the time of analysis. Humanely killed indicates mice killed for analysis before the development of an obvious phenotype. All mice developed neutrophilia (defined as more than 20% neutrophils; mean neutrophil percentage of control animals was 10% ± 3% WBCs, and the neutrophil percentage in control animals did not exceed 20%) after induction of BCR-ABL. Platelet counts (normal range, 300-900/nL) were not significantly elevated. Normal spleen weight in single- transgenic animals was 80 to 90 mg (n = 3). Thirty-one percent of all animals demonstrated a biphasic phenotype, consisting of neutrophilia, subsequent development of lymphoid tumors, and acute lymphoblastic leukemia reminiscent of blast crisis. Hgb indicates hemoglobin (normal range, 12-16 g/dL); LN, lymphadenopathy; BM, bone marrow; PB, peripheral blood; ND, not determined at time of death.

*

Normal range of WBC counts was 4000 to 10,000/μL.

Myeloid cells.

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