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Myc Is Essential for Transformation by TEL/Platelet-Derived Growth
Factor Receptor  (PDGFR)
Marie-Françoise Bourgeade,
Anne-Sophie Défachelles, and
Yvon E. Cayre
From U417 Institut de la Santé et de la Recherche
Médicale (INSERM), Hôpital Saint-Antoine, Paris, France;
and the Department of Microbiology/Immunology, Bluemle Life Sciences
Building, Thomas Jefferson University, Philadelphia, PA.
The t(5;12) translocation identified in patients with
chronic myelomonocytic leukemia (CMML)
encodes a TEL/platelet-derived growth factor receptor  (PDGFR) fusion protein. A key hypothesis for how the TEL/PDGFR
fusion protein would function as an oncogene is that it represents a
constitutively active version of the normal PDGFR. A link between
the function of the t(5;12)-encoded TEL/PDGFR fusion protein and Myc
expression is suggested by the fact that Myc is induced by PDGF and is
essential for entry of cells into the S phase of the cell cycle. We
here show that the kinase activity of TEL/PDGFR is necessary for
Ba/F3 cells to acquire interleukin-3 (IL-3) independence and that, in
contrast to their untransfected counterpart, Ba/F3 cells stably
transfected with TEL/PDGFR maintain a high level of Myc expression
after removal of IL-3. Using dominant negative mutants of Myc, we show
that a threshold of active Myc is essential for TEL/PDGFR to
transform Ba/F3 and Rat-1 cells. The findings that the kinase activity
of TEL/PDGFR and a threshold of active Myc are involved in
TEL/PDGFR transformation may allow for the development of
therapeutic strategies in patients with t(5;12)+ CMML
using specific inhibitors of the PDGFR kinase as well as compounds
designed to interfere specifically with Myc.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3333-3339
© 1998 by The American Society of Hematology.
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