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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1355-1363
Fusion of ETV6 to Neurotrophin-3 Receptor TRKC in
Acute Myeloid Leukemia With t(12;15)(p13;q25)
Mariko Eguchi,
Minenori Eguchi-Ishimae,
Arinobu Tojo,
Kazuhiro Morishita,
Katsuyuki Suzuki,
Yuko Sato,
Shiori Kudoh,
Kimio Tanaka,
Misao Setoyama,
Fumitaka Nagamura,
Shigetaka Asano, and
Nanao Kamada
From the Department of Cancer Cytogenetics and the Department of
Biochemistry and Biophysics, Research Institute for Radiation Biology
and Medicine, Hiroshima University, Hiroshima, Japan; the Department of
Hematology/Oncology, Institute of Medical Science, University of Tokyo,
Tokyo, Japan; the Biology Division, National Cancer Center Research
Institute, Tokyo, Japan; and the Division of Intractable Disease,
Research Institute, International Medical Center of Japan, Tokyo,
Japan.
Chromosome translocations involving band 12p13 are known to be
involved in a variety of hematologic malignancies, some of them
resulting in rearrangement of the ETV6/TEL gene. Applying the
fluorescence in situ hybridization (FISH) method, we found a cryptic
translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia
(AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A
patient-specific cDNA library was screened with ETV6 cDNA, and
a novel fusion transcript was identified between the ETV6 and
TRKC/NTRK3 gene located on 15q25. TRKC is a receptor
tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known
to be expressed broadly in neural tissues but not in hematologic cells,
so far. ETV6-TRKC chimeric transcript encoded the
pointed (PNT) domain of the ETV6 gene that fused to the
protein-tyrosine kinase (PTK) domain of the TRKC gene. Two
types of fusion transcript were determined, one that included the
entire PTK domain of TRKC and the other in which the
3'-terminal 462 bp of TRKC was truncated within the PTK
domain. Western blot analysis showed the expression of both chimeric
proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK
expressed in the leukemic cells may contribute to cellular
transformation by abnormally activating TRK signaling pathways.
Moreover, this is the first report on truncated neurotrophin receptors
associated in leukemia.
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