title: ETV6-LPXN fusion transcript generated by t(11;12)(q12.1;p13) in a patient with relapsing acute myeloid leukemia with NUP98-HOXA9.
abstract: ETV6, which encodes an ETS family transcription factor, is frequently rearranged in human leukemias. We show here that a patient with acute myeloid leukemia with t(7;11)(p15;p15) gained, at the time of relapse, t(11;12)(q12.1;p13) with a split ETV6 FISH signal. Using 3'-RACE PCR analysis, we found that ETV6 was fused to LPXN at 11q12.1, which encodes leupaxin. ETV6-LPXN, an in-frame fusion between exon 4 of ETV6 and exon 2 of LPXN, did not transform the interleukin-3-dependent 32D myeloid cell line to cytokine independence; however, an enhanced proliferative response was observed when these cells were treated with G-CSF without inhibition of granulocytic differentiation. The 32D and human leukemia cell lines each transduced with ETV6-LPXN showed enhanced migration towards the chemokine CXCL12. We show here for the first time that LPXN is a fusion partner of ETV6 and present evidence indicating that ETV6-LPXN plays a crucial role in leukemia progression through enhancing the response to G-CSF and CXCL12.
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iba
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Kanie
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Morishima
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mizuta
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kameyama
authors.affiliation: Division of Gene Expression Mechanism, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Akila
authors.initials: A
authors.lastname: Mayeda
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D050939:Gene Fusion; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C112251:LPXN protein, human; C465451:Nup98 protein, human; C097899:homeobox protein HOXA9