Molecular heterogeneity of the NUP98/HOXA9 fusion transcript in myelodysplastic syndromes associated with t(7;11)(p15;p15)

被引:38
作者
Hatano, Y
Miura, I
Nakamura, T
Yamazaki, Y
Takahashi, N
Miura, AB
机构
[1] Akita Univ, Sch Med, Dept Internal Med 3, Akita 0108543, Japan
[2] Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan
[3] JST, PRESTO, Tokyo, Japan
关键词
MDS; t(7; 11)(p15; p15); NUP98; HOXA9; fusion transcript;
D O I
10.1046/j.1365-2141.1999.01754.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The reciprocal translocation t(7;11)(p15;p15) has been reported as occurring mainly in acute myelogenous leukaemia (AML) and the acute phase of chronic myelogenons leukaemia (CML). This translocation in AML involves both the nucleoporin gene NUP98 on 11p15 and the homeobox: gene HOXA9 on 7p15. The invariant chimaeric NUP98/HOXA9 transcripts are a result of the fact that each breakpoint of the NUP98 and the corresponding breakpoint of the HOXA9 gene cluster occur within the same intron. Only one patient with myelodysplastic syndromes (MDS) carrying this chromosome aberration has been reported, but this study did not involve molecular analysis. We describe two patients with MDS associated with t(7;11): patient 1 was a Japanese man diagnosed with chronic myelomonocytic leukaemia; patient 2 was a Japanese woman with refractory anaemia with excess of blasts in transformation. Within a year both patients developed AML and showed multidrug resistance to chemotherapy, Southern blot analysis showed rearrangements of the NUP98 gene of the two patients and the HOXA9 gene of patient 2. Patient 1 had two types of the novel NUP98/HOXA9 fusion transcripts. Each of them lacked the common 141bp NUP98 exon which was contained in the NUP98/HOXA9 fusion transcripts detected in patient 2 and the reported AML cases. These data indicated that t(7:11) could determine the development of Various myeloid leukaemias and that the resultant chimaeric transcripts are heterogenous.
引用
收藏
页码:600 / 604
页数:5
相关论文
共 12 条
[1]   PROPOSALS FOR THE CLASSIFICATION OF THE MYELODYSPLASTIC SYNDROMES [J].
BENNETT, JM ;
CATOVSKY, D ;
DANIEL, MT ;
FLANDRIN, G ;
GALTON, DAG ;
GRALNICK, HR ;
SULTAN, C .
BRITISH JOURNAL OF HAEMATOLOGY, 1982, 51 (02) :189-199
[2]   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
[3]   Clinical, haematological and molecular studies in patients with chromosome translocation t(7;11): A study of four Chinese patients in Taiwan [J].
Huang, SY ;
Tang, JL ;
Liang, YJ ;
Wang, CH ;
Chen, YC ;
Tien, HF .
BRITISH JOURNAL OF HAEMATOLOGY, 1997, 96 (04) :682-687
[4]  
ISCN, 1995, INT SYST HUM CYT NOM
[5]   ECOTROPIC MURINE LEUKEMIA-VIRUS DNA CONTENT OF NORMAL AND LYMPHOMATOUS TISSUES OF BXH-2 RECOMBINANT INBRED MICE [J].
JENKINS, NA ;
COPELAND, NG ;
TAYLOR, BA ;
BEDIGIAN, HG ;
LEE, BK .
JOURNAL OF VIROLOGY, 1982, 42 (02) :379-388
[6]   PH+ ACUTE MYELOGENOUS LEUKEMIA WITH T(711)(P15P15) AND CLONAL EVOLUTION IN RELAPSE AFTER BONE-MARROW TRANSPLANTATION [J].
MIURA, I ;
NISHINARI, T ;
HASHIMOTO, K ;
NIMURA, T ;
TAKATSU, H ;
NIITSU, H ;
HIROKAWA, M ;
KUWAYAMA, A ;
NISHIMURA, S ;
MIURA, AB .
ACTA HAEMATOLOGICA, 1993, 90 (03) :148-150
[7]   Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia [J].
Nakamura, T ;
Largaespada, DA ;
Lee, MP ;
Johnson, LA ;
Ohyashiki, K ;
Toyama, K ;
Chen, SJ ;
Willman, CL ;
Chen, IM ;
Feinberg, AP ;
Jenkins, NA ;
Copeland, NG ;
Shaughnessy, JD .
NATURE GENETICS, 1996, 12 (02) :154-158
[8]   Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias [J].
Nakamura, T ;
Largaespada, DA ;
Shaughnessy, JD ;
Jenkins, NA ;
Copeland, NG .
NATURE GENETICS, 1996, 12 (02) :149-153
[9]   TRANSLOCATION BETWEEN CHROMOSOMES 7 AND 11 IN NONLYMPHOCYTIC NEOPLASIA [J].
OHYASHIKI, K ;
OHYASHIKI, JH ;
RYAN, DH ;
MILLER, KB ;
ITO, H ;
SANDBERG, AA .
CANCER GENETICS AND CYTOGENETICS, 1987, 26 (02) :191-197
[10]   THE PEPTIDE REPEAT DOMAIN OF NUCLEOPORIN NUP98 FUNCTIONS AS A DOCKING SITE IN TRANSPORT ACROSS THE NUCLEAR-PORE COMPLEX [J].
RADU, A ;
MOORE, MS ;
BLOBEL, G .
CELL, 1995, 81 (02) :215-222