Clonal characteristics of acute lymphoblastic cells derived from BCR/ABL p190 transgenic mice.
The clonal and immunophenotypic characteristics of blood leukemic cells from BCR/ABL p190 transgenic mice were investigated. All cell populations evaluated in vivo and in vitro had B-lymphocyte progenitor immunophenotypes. Immunoglobulin (JH) rearrangement patterns provided evidence for clonal diversification at different sites in vivo. Multiple clones were established in vitro from two of these mice (nos. 730 and 753). These cells expressed BCR/ABL p190 protein tyrosine kinase (PTK) and were highly malignant on transfer to secondary recipients. Cells independently cloned in vitro shared identical immunophenotypes and clonal IgH rearrangements, but these were distinct from those of the dominant clones in the mouse from which they were derived. Nevertheless, in vitro clones from mouse no. 753 had an abnormal karyotype (chromosome 14 trisomy) in common with the dominant clone in blood, providing evidence for a hierarchy or clonal selection in vivo and in vitro. Two sets of in vitro clones proliferated independently of exogenous growth factors and stroma and released autocrine interleukin 7 growth factor activity. These data provide evidence for rapid divergent clonal evolution and selection of B-cell progenitors initiated by BCR/ABL p190, followed by other, secondary genetic events mirroring similar changes in the equivalent, highly malignant human leukemia Philadelphia (Ph)-positive/B-precursor acute lymphoblastic leukemia (ALL).
Griffiths
S D
SD
Leukaemia Research Fund Centre, Chester Beatty Laboratories, London, UK.
Healy
L E
LE
Ford
A M
AM
Bennett
C A
CA
Voncken
J W
JW
Heisterkamp
N
N
Groffen
J
J
Greaves
M F
MF
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001483:Base Sequence; D002455:Cell Division; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007621:Karyotyping; D017493:Leukocyte Common Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D016044:Fusion Proteins, bcr-abl; D017493:Leukocyte Common Antigens