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Fusion of Huntingtin Interacting Protein 1 to Platelet-Derived Growth
Factor  Receptor (PDGFR) in Chronic Myelomonocytic Leukemia
With t(5;7)(q33;q11.2)
Theodora S. Ross,
Olivier A. Bernard,
Roland Berger, and
D. Gary Gilliland
From the Division of Hematology/Oncology, Brigham and Women's
Hospital and Division of Oncology, Dana-Farber Cancer Institute,
Boston, MA; the U 301 de L'Institut National de la Santé et de
la Recherche Medicale (INSERM) and SD 401 No. 301 CNRS, Institut de
Genetique Moleculaire, Paris, France; and the Howard Hughes Medical
Institute, Harvard Medical School, Boston, MA.
We report the fusion of the Huntingtin interactin protein 1 (HIP1) gene to the platelet-derived growth factor
 receptor (PDGFR) gene in a
patient with chronic myelomonocytic leukemia (CMML) with a
t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone
marrow cells with a PDGFR gene probe
demonstrated rearrangement of the PDGFR gene.
Anchored polymerase chain reaction using PDGFR
primers identified a chimeric transcript containing the HIP1
gene located at 7q11.2 fused to the PDGFR gene
on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid
screening for proteins that interact with Huntingtin, the mutated
protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFR fusion gene that encodes amino
acids 1 to 950 of HIP1 joined in-frame to the transmembrane and
tyrosine kinase domains of the PDGFR. The reciprocal
PDGFR/HIP1 transcript is not expressed.
HIP1/PDGFR is a 180-kD protein when expressed in the murine
hematopoietic cell line, Ba/F3, and is constitutively tyrosine
phosphorylated. Furthermore, HIP1/PDGFR transforms the Ba/F3 cells
to interleukin-3-independent growth. These data are consistent with an
alternative mechanism for activation of PDGFR tyrosine kinase
activity by fusion with HIP1, leading to transformation of
hematopoietic cells, and may implicate Huntingtin or HIP1 in the
pathogenesis of hematopoietic malignancies.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4419-4426
© 1998 by The American Society of Hematology.
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