Acute myeloid leukemia bearing t(7;11)(p15;p15) is a distinct cytogenetic entity with poor outcome and a distinct mutation profile: comparative analysis of 493 adult patients

被引：54

作者：

Chou, W-C ^{[1
,2
]}

Chen, C-Y ^{[1
]}

Hou, H-A ^{[1
]}

Lin, L-I ^{[3
]}

Tang, J-L ^{[1
]}

Yao, M. ^{[1
]}

Tsay, W. ^{[1
]}

Ko, B-S ^{[1
]}

Wu, S-J ^{[1
]}

Huang, S-Y ^{[1
]}

Hsu, S-C ^{[2
]}

Chen, Y-C ^{[2
]}

Huang, Y-N ^{[2
]}

Tseng, M-H ^{[1
]}

Huang, C-F ^{[1
]}

Tien, H-F ^{[1
]}

机构：

[1] Natl Taiwan Univ, Dept Internal Med, Natl Taiwan Univ Hosp, Taipei 100, Taiwan

[2] Natl Taiwan Univ, Dept Lab Med, Natl Taiwan Univ Hosp, Taipei 100, Taiwan

[3] Natl Taiwan Univ, Grad Inst Med Biotechnol, Coll Med, Taipei 100, Taiwan

来源：

LEUKEMIA | 2009年 / 23卷 / 07期

关键词：

NUP98-HOXA9; acute myeloid leukemia; t(7; 11)(p15; p15); CHRONIC MYELOGENOUS LEUKEMIA; CHROMOSOME-TRANSLOCATION T(7/11)(P15; P15); NUP98/HOXA9 FUSION TRANSCRIPT; CLINICAL-IMPLICATIONS; NUP98; GENE; TRILINEAGE MYELODYSPLASIA; MYELOMONOCYTIC LEUKEMIA; CHINESE PATIENTS; HOMEOBOX GENE; RAS MUTATION;

D O I：

10.1038/leu.2009.25

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98-HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger (P = 0.0076) and female (P = 0.0111), with almost all having the M2-subtype of AML (P < 0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P = 0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P = 0.003). The NUP98-HOXA9 fusion was strongly associated with KRAS and WT1 mutations (P = 0.015 and P = 0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98-HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group. Leukemia (2009) 23, 1303-1310; doi: 10.1038/leu.2009.25; published online 19 February 2009

引用

页码：1303 / 1310

页数：8

共 47 条

[1]

Ahuja HG, 2001, GENE CHROMOSOME CANC, V30, P410, DOI 10.1002/1098-2264(2001)9999:9999<::AID-GCC1108>3.0.CO

[2]

2-9

[3] The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9 [J].

Borrow, J ;

Shearman, AM ;

Stanton, VP ;

Becher, R ;

Collins, T ;

Williams, AJ ;

Dube, I ;

Katz, F ;

Kwong, YL ;

Morris, C ;

Ohyashiki, K ;

Toyama, K ;

Rowley, J ;

Housman, DE .

NATURE GENETICS, 1996, 12 (02) :159-167

[4] RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years [J].

Bowen, DT ;

Frew, ME ;

Hills, R ;

Gale, RE ;

Wheatley, K ;

Groves, MJ ;

Langabeer, SE ;

Kottaridis, PD ;

Moorman, AV ;

Burnett, AK ;

Linch, DC .

BLOOD, 2005, 106 (06) :2113-2119

[5] RUNX1 gene mutation in primary myelodysplastic syndrome -: the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome [J].

Chen, Chien-Yuan ;

Lin, Liang-In ;

Tang, Jih-Luh ;

Ko, Bo-Sheng ;

Tsay, Woei ;

Chou, Wen-Chien ;

Yao, Ming ;

Wu, Shang-Ju ;

Tseng, Mei-Hsuan ;

Tien, Hwei-Fang .

BRITISH JOURNAL OF HAEMATOLOGY, 2007, 139 (03) :405-414

[6] Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations [J].

Chou, W-C ;

Tang, J-L ;

Wu, S-J ;

Tsay, W. ;

Yao, M. ;

Huang, S-Y ;

Huang, K-C ;

Chen, C-Y ;

Huang, C-F ;

Tien, H-F .

LEUKEMIA, 2007, 21 (05) :998-1004

[7] Nucleophosmin mutations in De novo acute myeloid leukemia:: The age-dependent incidences and the stability during disease [J].

Chou, WC ;

Tang, JL ;

Lin, LI ;

Yao, M ;

Tsay, W ;

Chen, CY ;

Wu, SJ ;

Huang, CF ;

Chiou, RJ ;

Tseng, MH ;

Lin, DT ;

Lin, KH ;

Chen, YC ;

Tien, HF .

CANCER RESEARCH, 2006, 66 (06) :3310-3316

[8] Enforced expression of NUP98-HOXA9 in human CD34+ cells enhances stem cell proliferation [J].

Chung, Ki Y. ;

Morrone, Giovanni ;

Schuringa, Jan Jacob ;

Plasilova, Magdalena ;

Shieh, Jae-Hung ;

Zhang, Yue ;

Zhou, Pengbo ;

Moore, Malcolm A. S. .

CANCER RESEARCH, 2006, 66 (24) :11781-11791

[9] A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9 [J].

Dash, AB ;

Williams, IR ;

Kutok, JL ;

Tomasson, MH ;

Anastasiadou, E ;

Lindahl, K ;

Li, SG ;

Van Etten, RA ;

Borrows, J ;

Housman, D ;

Druker, B ;

Gilliland, DG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (11) :7622-7627

[10] Polycomb silencing blocks transcription initiation [J].

Dellino, GI ;

Schwartz, YB ;

Farkas, G ;

McCabe, D ;

Elgin, SCR ;

Pirrotta, V .

MOLECULAR CELL, 2004, 13 (06) :887-893

← 1 2 3 4 5 →