This is a significant improvement over cell culture 
strategies in which only a rare leukemia can be 
coaxed into continuous growth. The SCID mouse 
should be an important test model for evaluation of 
new therapeutic modalities in chronic and other my- 
elogenous leukemias. 
The unusual mechanism by which BCR appears to 
activate ABL stimulated further work to define the 
range of genetic alterations that can activate this 
member of the tyrosine kinase family. Alteration of 
the regulatory domain SH3 by deletion or insertion 
mutation was previously shown to activate the trans- 
forming potential of the ABL tyrosine kinase. Recent 
work in this laboratory has now demonstrated that 
exchange of SH2 domains with other members of 
the tyrosine kinase family or from non-kinase SH2- 
containing proteins is also sufficient to activate the 
ABL tyrosine kinase. This suggests that subtle 
changes in structure within these regulatory do- 
mains is sufficient for activation and should be con- 
sidered in other abnormal growth states associated 
with the ABL gene. 
Dr. Witte is also Professor of Microbiology and 
Molecular Genetics, holds the David Saxon Presi- 
dential Chair in Developmental Immunology, 
and is a member of the Molecular Biology Insti- 
tute at the University of California, Los Angeles. 
Books and Chapters of Books 
Witte, O.N., editor. 1992. Oncogenes in the Devel- 
opment of Leukemia. Cold Spring Harbor, NY: 
Cold Spring Harbor. {Cancer Surveys 15.) 
Witte, O.N., Kelliher, M., Muller, A., Pendergast, 
A.M., Gishizky, M., McLaughlin, J., Sawyers, C, 
Maru, Y., Shah, N., Denny, C, and Rosenberg, N. 
1991. Role of the BCR ABL oncogene in the 
pathogenesis of Philadelphia chromosome posi- 
tive leukemias. In Origins of Human Cancer: A 
Comprehensive Review (Brugge, J., Curran, T., 
Harlow, E., and McCormick, F., Eds.). Plainview, 
NY: Cold Spring Harbor, pp 521-526. 
Articles 
Gishizky, M.L., and Witte, O.N. 1992. Initiation of 
deregulated growth of multipotent hematopoi- 
etic progenitor cells by bcr-abl in vitro. Science 
256:836-839. 
Kelliher, M., Knott, A., McLaughlin, J., Witte, O.N., 
and Rosenberg, N. 1991. Diff'erences in onco- 
genic potency but not target cell specificity distin- 
guish the two forms of the BCR/ABL oncogene. 
Mol Cell Biol 1 1 :4710-47l6. 
Maru, Y., and Witte, O.N. 1991. The BCR gene 
encodes a novel serine/threonine kinase activity 
within a single exon. Cell 67:459-468. 
Sawyers, C.L., Gishizky, M.L., Quan, S., Golde, 
D.W., and Witte, O.N. 1992. Efficient propaga- 
tion of human blastic myeloid leukemias in the 
SCID mouse. Blood 79:2089-2098. 
IMMUNOLOGY 371 
