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The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. 总被引:6,自引:2,他引:4
The NUP98 gene is involved in 3 distinct chromosomal rearrangements, t(7;11)(p15;p15), t(2;11)(q31;p15), and inv(11)(p15q22); all of these NUP98 rearrangements have been identified in the malignant cells of patients with therapy-related acute myelogenous leukemia or myelodysplastic syndrome (t-AML/MDS). Here we report the cloning and characterization of a t(11;20)(p15;q11) translocation from patients with t-MDS. The breakpoint on chromosome 11p15 targets the NUP98 gene and results in the separation of the N-terminal FXFG repeats from the RNA-binding domain located in the C-terminus. The breakpoint on chromosome 20q11 occurs within the gene encoding human DNA topoisomerase I (TOP1). As a result, a chimeric mRNA encoding the NUP98 FXFG repeats fused to the body of DNA topoisomerase I is produced. These results indicate that NUP98 is a recurrent target in therapy-related malignancies, and that TOP1 is a previously unrecognized target for chromosomal translocations. 相似文献
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Takatoshi Aoki Toshihiro Miyamoto Shuro Yoshida Asataro Yamamoto Takuji Yamauchi Goichi Yoshimoto Yasuo Mori Kenjiro Kamezaki Hiromi Iwasaki Katsuto Takenaka Naoki Harada Koji Nagafuji Takanori Teshima Koichi Akashi 《International journal of hematology》2008,88(5):571-574
We report a 29-year-old Japanese male with acute myelogenous leukemia (AML)-M4 with a cryptic t(7;11)(p15;p15), in which a
chimeric NUP98-HOXA9 fusion was detected by polymerase chain reaction analysis and a chromosomal analysis showed 46,XY. The patient received intensive
chemotherapy and underwent autologous stem cell transplantation, and remission was confirmed by the disappearance of NUP98-HOXA9. However, 6 months after transplantation, the patient relapsed; NUP98-HOXA9 was detected again and karyotypic analysis revealed 46,XY, t(1;21)(p32;q22). Fluorescent in situ hybridization (FISH) analysis
using an AML1-ETO translocation dual probe, showed that the 21q22 breakpoint involved AML1 locus. A retrospective FISH analysis showed that t(1;21) was absent at onset. This is the first reported case with AML who
had a cryptic t(7;11)(p15;p15), and additionally acquired t(1;21)(p32;q22) at relapse. 相似文献
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Yoko Mizoguchi Naoto Fujita Tomohiko Taki Yasuhide Hayashi Kazuko Hamamoto 《American journal of hematology》2009,84(5):295-297
The t(7;11)(p15;p15) translocation has been reported as a rare and recurrent chromosomal abnormality in acute myeloid leukemia (AML) patients. The NUP98‐HOXA9 fusion gene with t(7;11)(p15;p15) was identified and revealed to be essential for leukemogenesis and myeloproliferative disease. To date, t(7;11)(p15;p15) with NUP98‐HOXA11 fusion has been reported only in one case of ph‐negative chronic myeloid leukemia (CML). Here, we report a case of a 3‐year‐old girl with juvenile myelomonocytic leukemia (JMML) carrying t(7;11)(p15;p15) abnormality with NUP98‐HOXA11 fusion. AML chemotherapy followed by bone marrow transplantation (BMT) was found to be effective in treating this disorder, and she remains in complete remission for 3 years after BMT. We suggest the possibility that AML chemotherapy might be effective for treating JMML with t(7;11)(p15;p15) abnormality and NUP98‐HOXA11 fusion. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Ishikawa M Yagasaki F Okamura D Maeda T Sugahara Y Jinnai I Bessho M 《International journal of hematology》2007,86(3):238-245
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Mecucci C La Starza R Negrini M Sabbioni S Crescenzi B Leoni P Di Raimondo F Krampera M Cimino G Tafuri A Cuneo A Vitale A Foà R 《British journal of haematology》2000,109(4):788-793
Two cases of T acute lymphoblastic leukaemia (T-ALL) with an identical t(4;11)(q21;p15) translocation were identified within a prospective study on the biological and clinical features of adult ALL patients enrolled into the therapeutic protocol ALL0496 of the GIMEMA Italian Group. In both cases, the molecular characterization showed an involvement of the NUP98 gene on 11p15 which rearranges with the RAP1GDS1 gene on 4q21. The morphological and immunological features of the leukaemic cells, as well as the clinical behaviour and response to induction therapy, were the same in both patients. Based on the available data, the t(4;11)(q21;p15) translocation involving the NUP98-RAP1GDS1 fusion gene emerges as a new highly specific genetic abnormality that characterizes a subset of T-ALL. 相似文献
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Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia 总被引:2,自引:0,他引:2
Jankovic D Gorello P Liu T Ehret S La Starza R Desjobert C Baty F Brutsche M Jayaraman PS Santoro A Mecucci C Schwaller J 《Blood》2008,111(12):5672-5682
We have studied a patient with acute myeloid leukemia (AML) and t(10;11)(q23;p15) as the sole cytogenetic abnormality. Molecular analysis revealed a translocation involving nucleoporin 98 (NUP98) fused to the DNA-binding domain of the hematopoietically expressed homeobox gene (HHEX). Expression of NUP98/HHEX in murine bone marrow cells leads to aberrant self-renewal and a block in normal differentiation that depends on the integrity of the NUP98 GFLG repeats and the HHEX homeodomain. Transplantation of bone marrow cells expressing NUP98/HHEX leads to transplantable acute leukemia characterized by extensive infiltration of leukemic blasts expressing myeloid markers (Gr1+) as well as markers of the B-cell lineage (B220+). A latency period of 9 months and its clonal character suggest that NUP98/HHEX is necessary but not sufficient for disease induction. Expression of EGFP-NUP98/HHEX fusions showed a highly similar nuclear localization pattern as for other NUP98/homeodomain fusions, such as NUP98/HOXA9. Comparative gene expression profiling in primary bone marrow cells provided evidence for the presence of common targets in cells expressing NUP98/HOXA9 or NUP98/HHEX. Some of these genes (Hoxa5, Hoxa9, Flt3) are deregulated in NUP98/HHEX-induced murine leukemia as well as in human blasts carrying this fusion and might represent bona fide therapeutic targets. 相似文献
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Suzuki A Ito Y Sashida G Honda S Katagiri T Fujino T Nakamura T Ohyashiki K 《British journal of haematology》2002,116(1):170-172
We encountered a patient with Philadelphia-negative chronic myeloid leukaemia, with t(7;11)(p15;p15), in whom acute leukaemia phase (acute myeloid leukaemia-M2 morphology) developed within a short period. We detected a novel gene fusion between NUP98 and HOXA11 both in the chronic phase and in the acute leukaemia phase in this case. Although it is well known that a fusion of NUP98-HOXA9 in myeloid malignancies is created by the t(7;11)(p15;p15), this case suggests the possibility that HOXA11 might be another partner gene for NUP98 in t(7;11)(p15;p15) leukaemia. 相似文献
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Naoki Kakazu Isaku Shinzato Yasuhito Arai Saori Gotoh Akiko Matsushita Takayuki Ishikawa Kenichi Nagai Takayuki Takahashi Tatsuji Ohno Takayuki Tsuchiya Misao Ohki Tatsuo Abe 《International journal of hematology》2001,74(1):53-57
We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia. 相似文献