1.A case of Allgrove syndrome with achalasia of cardia as its first clinical phenotype caused by a new mutation of AAAS gene.
Li Ya XIONG ; Pei Yu CHEN ; Jing XIE ; Lu REN ; Hong Li WANG ; Yang CHENG ; Pei Qun WU ; Hui Wen LI ; Si Tang GONG ; Lan Lan GENG
Chinese Journal of Pediatrics 2023;61(7):648-650
5.Effects of gambogic acid on the regulation of nucleoporin Nup88 in U937 cells.
Wenxiu, SHU ; Yan, CHEN ; Jing, HE ; Guohui, CUI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(4):388-92
In order to investigate the anti-leukemia effects of gambogic acid (GA) and its relation to the regulation of nucleoporin Nup88 in U937 cells in vitro, the inhibitory effect of GA on the growth of U937 cells was examined by using MTT assay. Apoptosis was detected by Annexin-V FITC/PI double-labeled cytometry. Cell cycle regulation was studied by propidium iodide method. Both flow cytometry (FCM) and RT-PCR were employed to assess the expression of Nup88, and the localization of Nup88 was determined by confocal microscopy. The results indicated that GA had strong inhibitory effect on cell proliferation and apoptosis induction activity in U937 cells in vitro in a time-and dose-dependent manner. The 24-h IC(50) value was (1.019+/-0.134) mg/L. Moreover, GA induced arrest of U937 cells in G(0)/G(1) phase. Over-expression of Nup88 was found in U937 cells, whereas GA could significantly down-regulate both the protein and mRNA levels of Nup88. Nup88 was diffusely distributed between nucleus and cytoplasm and was located at the cytoplasmic side of nuclear rim, and occasionally in cytoplasm. It is suggested that GA exerts its anti-leukemia effects by regulating the expression and distribution of nucleoporin Nup88. It promises to be new agent for the treatment of acute leukemia.
Antineoplastic Agents, Phytogenic/*pharmacology
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Apoptosis/drug effects
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Cell Proliferation/drug effects
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Nuclear Pore Complex Proteins/genetics
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Nuclear Pore Complex Proteins/*metabolism
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RNA, Messenger/genetics
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RNA, Messenger/metabolism
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U937 Cells
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Xanthones/*pharmacology
6.Overexpression of CHIP in chronic myeloid leukemia K562 cells induces mitotic abnormality.
Ying GAO ; Yan WANG ; Xu-Hui ZHANG ; Guo-Zhu CHEN ; Zhi-Yan DU ; Yuan-Ji XU ; Xiao-Dan YU
Journal of Experimental Hematology 2008;16(4):763-767
This study was aimed to investigate the possible influence of a novel E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70/Hsp70-interacting protein) on biological characteristics of cancer cells. Stable overexpression models in CML K562 cells were established via lipofectamine-mediated wild type CHIP and its TPR or U-box deletion mutants gene transfection. Followed G418 pressure selection, K562-CHIP stable transfected cell clones were obtained by limited dilution. The proliferation status and cell cycle were observed by MTT assay and FACS. The expression of related proteins and morphological changes were detected by Western blot and Wright-Giemsa staining. The results showed that overexpression of wild type CHIP did not inhibit cell proliferation, but slightly increased cell ratio of G(2)/M phase. CHIP gene had no effect on the stability of BCR-ABL kinase protein. HDAC inhibitor FK228-induced BCR-ABL degradation did not enhanced by CHIP. Notably the enlarged cells and abnormal mitotic cells remarkably increased in K562 WT-CHIP cells, indicating that CHIP may involve in the regulation of mitotic process. It is concluded that wild type CHIP induces mitotic abnormity in K562 cells.
Heat-Shock Proteins
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genetics
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metabolism
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Humans
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K562 Cells
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Mitosis
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Nuclear Pore Complex Proteins
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genetics
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metabolism
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Proto-Oncogene Proteins
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genetics
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metabolism
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Sequence Deletion
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Transfection
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Ubiquitin-Protein Ligases
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genetics
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metabolism
7.Effect of deguelin on expression of nup98 in K562 cells.
Qiu-Ling WU ; Yan CHEN ; Wei-Hua CHEN ; Jing HE
Journal of Experimental Hematology 2007;15(1):25-28
The study was purposed to investigate the effect of deguelin on expression of nucleoporin 98 (nup98) in leukemia K562 cells. MTT assay was used to assess the effects of deguelin on cell proliferation. FCM and RT-PCR were used to analyze the changes of nup98 mRNA and protein in K562 cells after treating with deguelin. The results showed that deguelin inhibited the proliferation of K562 cells in a time- and dose-dependent manner; mean fluorescence intensity of nup98 in blank group (34.22 +/- 1.63) was significantly higher than that in control group (2.83 +/- 0.02, P < 0.01), 10 nmol/L deguelin could significantly inhibit the expression of nup98 protein; 10 nmol/L could not inhibit the expression of nup98 mRNA, 20, 40, 80, 160 nmol/L deguelin could significantly inhibit the expression of nup98 mRNA in a dose-dependant manner. It is concluded that deguelin inhibits the proliferation of K562 cell through inhibiting the expression of nup98, and may be considered as a new target for therapy of acute leukemia.
Antineoplastic Agents, Phytogenic
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pharmacology
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Cell Proliferation
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Dose-Response Relationship, Drug
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Humans
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K562 Cells
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Nuclear Pore Complex Proteins
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biosynthesis
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genetics
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RNA, Messenger
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biosynthesis
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genetics
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Rotenone
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analogs & derivatives
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pharmacology
8.Clinical Characteristics and Prognosis of Adult Acute Myeloid Leukemia with NUP98 Gene Rearrangement.
Ning LU ; Yi DING ; Yong-Li WU ; Li-Li WANG ; Yu JING ; Hong-Hua LI ; Meng LI
Journal of Experimental Hematology 2021;29(5):1450-1455
OBJECTIVE:
To investigate the clinical characteristics, outcomes and prognosis of adult acute myeloid leukemia (AML) patients with NUP98 gene rearrangement.
METHODS:
The clinical data of adult AML patients with NUP98 gene rearrangement from January 2015 to December 2019 were retrospectively analyzed, including clinical characteristics, laboratory examination, genetic anomaly, treatment strategy and survival.
RESULTS:
A total of 15 patients with NUP98 gene rearrangement were detected in 410 adult AML patients (3.7%). The ratio of male to female among 15 patients was 1.1∶1, and the median age was 43 (17-76) years old. The main FAB types were M2 and M4/M5, and including one unclassified. According to the genetic prognosis, 11 cases were intermediate risk, while 4 cases were high risk. The main type of NUP98 gene rearrangement was NUP98-HOXA9 (13/15, 86.7%). 10 patients underwent next generation sequencing, in which 5 patients showed epigenetic gene mutations, 3 patients showed FLT3-ITD or WT1 mutations, and 2 patients showed no mutation. After induction therapy, 13 of 15 patients achieved complete remission(CR). 7 of 8 patients with standard induction therapy achieved CR. 7 elder or intolerance patients with demethylation drug and chemotherapy all achieved CR. The median follow-up time was 28 months. The median OS of 15 the patients was 31.5 months (95% CI 10.7%-52.2%), and the median OS of the patients in non-allogeneic hematopoietic stem cell transplantation (Allo-HSCT) group was 18.5 months (95% CI 17.8%-19.1%). The median OS was not reached for the patients in the Allo-HSCT group.
CONCLUSION
Allo-HSCT can significantly improve the prognosis of AML patients with NUP98 rearrangement. NUP98 rearrangement can be accompanied by epigenetic gene mutations. For the elderly or patients who do not tolerate standard induction therapy, demethylation drugs combined with chemotherapy can achieve good outcomes.
Adolescent
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Adult
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Aged
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Female
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Gene Rearrangement
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Humans
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Leukemia, Myeloid, Acute/genetics*
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Male
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Middle Aged
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Nuclear Pore Complex Proteins/genetics*
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Prognosis
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Retrospective Studies
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Young Adult
9.Gene rearrangement pattern of immunoglobulin and T-cell receptor (Ig/TR) and its clinical characteristics in children with SET-NUP214 fusion gene-positive leukemia/lymphoma.
Wei-Jing LI ; Lei CUI ; Chao GAO ; Xiao-Xi ZHAO ; Shu-Guang LIU ; Yan-Ping XIN ; Rui-Dong ZHANG ; Da-Wei ZHANG ; Bin WANG ; Zhi-Gang LI ; Min-Yuan WU
Journal of Experimental Hematology 2011;19(6):1362-1367
The purpose of this study was to analyze the gene rearrangement pattern of immunoglobulin and T-cell receptor (Ig/TR) and its clinical characteristics in three children with SET-NUP214 fusion gene positive leukemia/lymphoma. The transcript of SET-NUP214 fusion gene was detected by RT-nested PCR. The pattern of Ig/TR gene rearrangement was analyzed by using the BIOMED-2 multiplex PCR assays. Allelic-specific primers were designed for further monitoring the minimal residual disease (MRD). The results indicated that the fusion site located between exon 7 of SET and exon 18 of NUP214 at mRNA level in the three patients. The diagnoses were made as the mixed phenotype of acute leukemia (MPAL) for patients 1, acute T-lymphoblastic leukemia (T-ALL) for patients 2, and stage IV T-lymphoblastic lymphoma (T-LBL) for patients 3, respectively. Patient 1 responded to chemotherapy very poorly and relapsed at month 6 after hematopoietic stem cell transplantation. Patient 2 had high MRD (> 10(-2)) at the end of inducing remission therapy (day 33) which implied poor outcome, and died of toxic epidermal necrolysis and sequent serious infection. Patient 3 achieved hematological complete remission (CR) and MRD negative at day 15 and day 33 respectively. The duration of CR lasted for 30 months. Clonal TR gene rearrangements were detected in all the three patients. The rearrangements of TRD, TRG and TRB were found in patient 1 and 3. The rearrangements of TRD, TRB, IgH and IgK Kde were detected in patient 2. All the 6 TRB rearrangements detected were incomplete rearrangements, whereas 85.7% and 14.3% of the TRD, and TRG rearrangements were complete and incomplete, respectively. It is concluded that the transformation of SET-NUP214(+) leukemia/lymphoma cells may occur after the rearrangements of TRD and TRG and shortly after TRB rearrangement. The leukemia/lymphoma cells of patient 1 and 2 are more immature which may be related with poor outcome or response to chemotherapy.
Child
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Female
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Gene Fusion
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Gene Rearrangement, T-Lymphocyte
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Histone Chaperones
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genetics
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Humans
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Immunoglobulins
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genetics
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Male
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Neoplasm, Residual
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diagnosis
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genetics
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Nuclear Pore Complex Proteins
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genetics
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Oncogene Proteins, Fusion
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genetics
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
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genetics
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Transcription Factors
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genetics
10.Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome.
A Ri CHO ; Keum Jin YANG ; Yoonsun BAE ; Young Yil BAHK ; Eunmin KIM ; Hyungnam LEE ; Jeong Ki KIM ; Wonsang PARK ; Hyanshuk RHIM ; Soo Young CHOI ; Tsuneo IMANAKA ; Sungdae MOON ; Jongbok YOON ; Sungjoo Kim YOON
Experimental & Molecular Medicine 2009;41(6):381-386
Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia-addisonianism-alacrima syndrome (AAAS) gene which encodes a tryptophan aspartic acid (WD) repeat-containing protein named alacrima-achalasia-adrenal insufficiency neurologic disorder (ALADIN). Northern blot analysis shows that the 2.1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas. We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. Furthermore, biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane. The mutations S544G and S544X show that alteration of S544 residue affects correct targeting of ALADIN to the nuclear membrane.
Adrenal Insufficiency/*genetics
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Antibodies/immunology
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Cloning, Molecular
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DNA, Complementary/genetics
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Esophageal Achalasia/*genetics
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Gene Expression Profiling
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Hela Cells
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Humans
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Lacrimal Apparatus Diseases/*genetics
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins/*analysis/*genetics/immunology
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Nuclear Pore/chemistry
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Nuclear Pore Complex Proteins/*analysis/*genetics/immunology
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RNA, Messenger/analysis/genetics
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Syndrome
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Tissue Distribution