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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukaemias. This result, combined with the mapping of the HOXA locus to human chromosome 7p15, suggested that one of the HOXA genes might be involved in the t(7;11)(p15;p15) translocation found in some human myeloid leukaemia patients. Here we show that in three patients with t(7;11), the chromosome rearrangement creates a genomic fusion between the HOXA9 gene and the nucleoporin gene NUP98 on chromosome 11p15. The translocation produces an invariant chimaeric NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in frame to HOXA9. These studies identify HOXA9 as an important human myeloid leukaemia gene and suggest an important role for nucleoporins in human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia.
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PMID:Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. 856 53

Chromosomal abnormalities involving the 11p15 or 11q22-23 bands have been reported in several types of human neoplasms including hematopoietic malignancies. The abnormalities are observed in therapy-related malignancies and less frequently in de novo myeloid malignancies. Abnormality of the MLL gene located on chromosome 11q23 has been well known in therapy-related myeloid malignancies, but it has been reported only recently that the inv(11)(p15q22) in de novo or therapy-related myeloid malignancies results in the fusion of NUP98 on chromosome 11p15 and DDX10 on chromosome 11q22. NUP98 is a nucleoporin that composes the nuclear pore complex and is the target gene in leukemia with the t(7;11)(p15;p15). The DDX10 gene encodes a putative adenosine triphosphate-dependent DEAD box RNA helicase. Here we present another patient with acute myelocytic leukemia (M4) transformed from chronic myelomonocytic leukemia with the inv(11) chromosome who had been treated with etoposide for a germ cell tumor. By reverse transcription polymerase chain reaction (RT-PCR) of the RNA from the leukemic cells of the patient, DDX10-NUP98 and NUP98-DDX10 fusion transcripts were detected. Our case confirms that the inv(11) is a rare chromosomal translocation that is associated with therapy-related or de novo myeloid malignancy and involves NUP98 and DDX10 but not MLL. RT-PCR of the fusion transcripts might be applied to the detection of a small number of leukemic cells in the bone marrow or blood of patients in remission or in the cells harvested for autologous transplantation.
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PMID:The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts. 1022 53

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 myelogenous 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 141 bp 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.
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PMID:Molecular heterogeneity of the NUP98/HOXA9 fusion transcript in myelodysplastic syndromes associated with t(7;11)(p15;p15). 1058 65

We describe a case of an acute myelogenous leukemia (AML) associated with t(1;11) (q23;p15), which is a novel simple variant translocation of t(7;11)(p15;p15). The patient was a Japanese man who had a history of non-Hodgkin lymphoma (NHL) and received MACOP-B combination chemotherapy. Fifteen months after the completion of the treatment, the patient developed AML (M2), which was regarded as a therapy-related leukemia. Cytogenetic study of bone marrow cells showed t(1;11). Although he achieved complete remission by combination chemotherapy, a relapse of NHL and gastric cancer were revealed in the course of the consolidation chemotherapy for AML. The NHL was considered a histological conversion from follicular lymphoma because lymphoma cells carried t(14;18) (q32;q21) and were strongly positive for BCL2 protein. Translocation (1;11), together with AML having t(7;11) or inv(11) involving 11p15, shows that 11p15 is a common acceptor site of these chromosome aberrations and suggests the significance of the NUP98 gene located in 11p15 in therapy-related leukemia.
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PMID:Translocation (1;11)(q23;p15), a novel simple variant of translocation (7;11)(p15;p15), in a patient with AML (M2) accompanied by non-Hodgkin lymphoma and gastric cancer. 1070 Aug 60

The t(7;11)(p15;p15) translocation is a recurrent aberration observed in acute myeloblastic leukaemia (AML) and chronic myelogenous leukaemia (CML). It has been shown that the NUP98 gene at 11p15 is fused with the HOXA9 gene at 7p15 in AML with t(7;11). We report the first case with CML expressing the NUP98/HOXA9 fusion transcript. A 27-year-old Japanese man was initially diagnosed as in the chronic phase of Philadelphia-positive CML. At the diagnosis of myeloid blast crisis, the karyotype evolved to 46, XY, t(7;11)(p15;p15), t(9;22)(q34;q11). Reverse transcriptase polymerase chain reaction identified the NUP98/HOXA9 transcript, suggesting that the NUP98/HOXA9 fusion protein could play a critical role in the progression to blast crisis.
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PMID:Expression of the NUP98/HOXA9 fusion transcript in the blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia with t(7;11)(p15;p15). 1084 35

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.
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PMID:t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia. 1092 31

We report a case of de novo acute myelomonocytic leukaemia with the t(2;11)(q31;p15) translocation in a Japanese female infant. The NUP98-HOXD13 fusion transcript generated by the translocation was detected in the patient's bone marrow cells by reverse transcription-polymerase chain reaction (RT-PCR). Additionally, ectopic expression of the normal allele of the HOXD13 gene was observed in this patient, suggesting that it might be associated with leukaemogenic development. This case is the third report of t(2;11) leukaemia with NUP98-HOXD13 and the first report showing that NUP98 rearrangements are associated with infant leukaemia, as well as therapy-related acute myelogenous leukaemia or myelodysplastic syndrome.
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PMID:Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia. 1093 Oct

We report the characterization of a rare chromosomal translocation, a t(2;11)(q31;p15), which occurred in a patient with de novo acute myeloid leukemia (AML-M4). By 3'-RACE and RT-PCR analyses, two kinds of NUP98-HOXD13 fusion transcript were detected. In addition, we identified a novel fusion transcript, NUP98-FN1, in the same patient. Ectopic expression of the wild-type HOXD13 gene was also observed in the patient, suggesting that HOXD13 contributes to the development of this type of leukemia. The NUP98-HOXD13 fusion transcript was predicted to encode a 552 or 569-amino acid protein containing the Phe-Gly (FG) repeat region of NUP98 and the homeodomain of HOXD13. The NUP98-FN1 fusion transcript was predicted to encode a 482 or 499-amino acid protein consisting of the same N-terminal region of NUP98 and a C-terminal region of 12 amino acids derived from a previously unidentified sequence. We isolated and characterized the chromosomal breakpoints. The breakpoint at 11p15 is mapped within a LINE repetitive element in a 9 kb intron of NUP98, and more than 60% of the sequenced 3 kb region surrounding the breakpoint junction consists of repetitive elements. The other breakpoint at 2q31 is in an intron of FN1, which is located 7 kb upstream of HOXD13, and the repetitive sequence content of the breakpoint junction is low. Local sequence duplications at genomic breakpoints suggest that the t(2;11) translocation is mediated through staggered double-strand DNA breaks. These results throw light on the mechanisms responsible for the generation of t(2;11) translocation and on the processes leading to t(2;11) leukemia.
Leukemia 2000 Sep
PMID:Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation. 1099 9

Here we describe hemopoietic chimeras serving as a mouse model for NUP98-HOXA9-induced leukemia, which reproduced several of the phenotypes observed in human disease. Mice transplanted with bone marrow cells expressing NUP98-HOXA9 through retroviral transduction acquire a myeloproliferative disease (MPD) and eventually succumb to acute myeloid leukemia (AML). The NUP98 portion of the fusion protein was shown to be responsible for transforming a clinically silent pre-leukemic phase observed for Hoxa9 into a chronic, stem cell-derived MPD. The co-expression of NUP98-HOXA9 and Meis1 accelerated the transformation of MPD to AML, identifying a genetic interaction previously observed for Hoxa9 and Meis1. Our findings demonstrate the presence of overlapping yet distinct molecular mechanisms for MPD versus AML, illustrating the complexity of leukemic transformation.
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PMID:NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice. 1115 42

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.
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PMID:Involvement of the NUP98 gene in a chromosomal translocation t(11;20)(p15;q11.2) in a patient with acute monocytic leukemia (FAB-M5b). 1153 Aug 5


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