PMID- 9949179
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20231213
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 4
DP  - 1999 Feb 15
TI  - Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with 
      t(12;15)(p13;q25).
PG  - 1355-63
AB  - 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.
FAU - Eguchi, M
AU  - Eguchi M
AD  - Department of Cancer Cytogenetics, Research Institute for Radiation Biology and 
      Medicine, Hiroshima University, Hiroshima, Japan.
FAU - Eguchi-Ishimae, M
AU  - Eguchi-Ishimae M
FAU - Tojo, A
AU  - Tojo A
FAU - Morishita, K
AU  - Morishita K
FAU - Suzuki, K
AU  - Suzuki K
FAU - Sato, Y
AU  - Sato Y
FAU - Kudoh, S
AU  - Kudoh S
FAU - Tanaka, K
AU  - Tanaka K
FAU - Setoyama, M
AU  - Setoyama M
FAU - Nagamura, F
AU  - Nagamura F
FAU - Asano, S
AU  - Asano S
FAU - Kamada, N
AU  - Kamada N
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 12
MH  - *Chromosomes, Human, Pair 15
MH  - DNA-Binding Proteins/*genetics
MH  - Gene Rearrangement
MH  - Humans
MH  - Leukemia, Myeloid/*genetics
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Proto-Oncogene Proteins c-ets
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Receptor, trkC
MH  - Receptors, Nerve Growth Factor/*genetics
MH  - *Repressor Proteins
MH  - Transcription Factors/*genetics
MH  - *Translocation, Genetic
MH  - ETS Translocation Variant 6 Protein
EDAT- 1999/02/09 00:00
MHDA- 1999/02/09 00:01
CRDT- 1999/02/09 00:00
PHST- 1999/02/09 00:00 [pubmed]
PHST- 1999/02/09 00:01 [medline]
PHST- 1999/02/09 00:00 [entrez]
AID - S0006-4971(20)48774-9 [pii]
PST - ppublish
SO  - Blood. 1999 Feb 15;93(4):1355-63.