ETV6-LPXN Fusion Transcript Generated by t(11;12)(q12.1;p13) in a Patient With Relapsing Acute Myeloid Leukemia With NUP98-HOXA9

被引:12
作者
Abe, Akihiro [1 ]
Yamamoto, Yukiya [1 ]
Iba, Sachiko [1 ]
Kanie, Tadaharu [1 ]
Okamoto, Akinao [1 ]
Tokuda, Masutaka [1 ]
Inaguma, Yoko [1 ]
Yanada, Masamitsu [1 ]
Morishima, Satoko [1 ]
Mizuta, Shuichi [1 ]
Akatsuka, Yoshiki [1 ]
Okamoto, Masataka [1 ]
Kameyama, Toshiki [2 ]
Mayeda, Akila [2 ]
Emi, Nobuhiko [1 ]
机构
[1] Fujita Hlth Univ, Dept Hematol, Toyoake, Aichi 4701192, Japan
[2] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Gene Express Mech, Toyoake, Aichi 4701192, Japan
关键词
ACUTE MYELOGENOUS LEUKEMIA; PROSTATE-CANCER; TYROSINE PHOSPHORYLATION; FOCAL ADHESION; CELL-LINE; LEUPAXIN; KINASE; RECEPTOR; GENE; PROTEIN;
D O I
10.1002/gcc.22327
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 30-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. (C) 2015 Wiley Periodicals, Inc.
引用
收藏
页码:242 / 250
页数:9
相关论文
共 33 条
[31]   Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system [J].
Weinberg, Olga K. ;
Seetharam, Mahesh ;
Ren, Li ;
Seo, Katie ;
Ma, Lisa ;
Merker, Jason D. ;
Gotlib, Jason ;
Zehnder, James L. ;
Arber, Daniel A. .
BLOOD, 2009, 113 (09) :1906-1908
[32]   Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML [J].
Zaitseva, Lyubov ;
Murray, Megan Y. ;
Shafat, Manar S. ;
Lawes, Matthew J. ;
MacEwan, David J. ;
Bowles, Kristian M. ;
Rushworth, Stuart A. .
ONCOTARGET, 2014, 5 (20) :9930-9938
[33]   Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML [J].
Zeng, Zhihong ;
Shi, Yue Xi ;
Samudio, Ismael J. ;
Wang, Rui-Yu ;
Ling, Xiaoyang ;
Frolova, Olga ;
Levis, Mark ;
Rubin, Joshua B. ;
Negrin, Robert R. ;
Estey, Elihu H. ;
Konoplev, Sergej ;
Andreeff, Michael ;
Konopleva, Marina .
BLOOD, 2009, 113 (24) :6215-6224