t(11;17)(p15;q21) NUP98/?
2015-12-01 Nicolas Duployez , Stéphanie Struski , Guillaume Grzych , Catherine Roche-Lestienne , Frédérique Payet Affiliation1.Institut de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU Lille (FP, ND, GG, CRL); Institut Universitaire du Cancer Toulouse - Oncopole, Laboratoire d hématologie /Plateau Technique Hématologie-Oncologie, 31059 TOULOUSE Cedex 9 (SS). [email protected]; [email protected]; [email protected]; [email protected]
Abstract
Review on t(11;17)(p15;q21) NUP98/?, with data on clinics, and the genes involved.
Clinics and Pathology
Disease
Myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML)
Clinics
3 cases of paediatric AML (sex ratio 1M/2F) with the t(11;17)(p15;q21) have been reported , two AML M4 cases (aged 3 and 4 years), and one AML M0 (aged 18 years). No treatment and evolution data available (Nishiyama et al., 1999; Kerndrup and Kjeldsen 2001; Forestier et al., 2003).
One MDS case with isolated t(11;17)(p15;q21) after neuroblastoma chemotherapy has been reported, a 8 years old girl. This patient achieved complete remission after bone marrow transplantation, but no data about induction treatment and response were reported. The patient died of this neuroblastoma ((Nishiyama et al., 1999).
In adult, only one case reported this translocation implicating NUP98 , a 86 year old man. Blasts CD34-, HLA-DR+ (78%), CD33+ (99%), CD13+ (99%), CD14+ (98%), CD15+ (95%). Because of high advanced age, the treatment was based on transfusions and HYDREA to control leukocytosis and cytopenias with no complete remission (Duployez et al., 2015).
One MDS case with isolated t(11;17)(p15;q21) after neuroblastoma chemotherapy has been reported, a 8 years old girl. This patient achieved complete remission after bone marrow transplantation, but no data about induction treatment and response were reported. The patient died of this neuroblastoma ((Nishiyama et al., 1999).
In adult, only one case reported this translocation implicating NUP98 , a 86 year old man. Blasts CD34-, HLA-DR+ (78%), CD33+ (99%), CD13+ (99%), CD14+ (98%), CD15+ (95%). Because of high advanced age, the treatment was based on transfusions and HYDREA to control leukocytosis and cytopenias with no complete remission (Duployez et al., 2015).
Cytogenetics
Implication of NUP98 in the t(11;17) by FISH, using RP11-120E20 (3NUP98, in red) and RP11-438N5 (5NUP98, in green) BAC probes. Arrows indicate the der(11) and der(17) chromosomes.
Probes
RP11-120E20 and RP11-438N5
Genes Involved and Proteins
Note
NUP98 is implicated in structural chromosome abnormalities with numerous patners.
Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Protein description
Nucleoporin 98, is a 98 kDa component of the nuclear pore complex involved in nucleo-cytoplasmic transport.
Result of the Chromosomal Anomaly
Description
5 NUP98 - 3 partner
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 39323480 | 2024 | NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities. | 191 |
| 32766874 | 2020 | Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies. | 167 |
| 38174649 | 2023 | Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression. | 156 |
| 21948299 | 2011 | NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights. | 152 |
| 19577736 | 2009 | Nuclear pore proteins and cancer. | 151 |
| 28221134 | 2017 | Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9. | 146 |
| 37388925 | 2023 | Biomolecular Condensates in Myeloid Leukemia: What Do They Tell Us? | 131 |
| 38443661 | 2024 | Acute myeloid leukemia with rare recurring translocations-an overview of the entities included in the international consensus classification. | 127 |
| 35107131 | 2022 | Misregulation of Nucleoporins 98 and 96 leads to defects in protein synthesis that promote hallmarks of tumorigenesis. | 124 |
| 38649536 | 2024 | A checkpoint function for Nup98 in nuclear pore formation suggested by novel inhibitory nanobodies. | 122 |
| 39273335 | 2024 | Interdependence between Nuclear Pore Gatekeepers and Genome Caretakers: Cues from Genome Instability Syndromes. | 117 |
| 36257947 | 2022 | A simple thermodynamic description of phase separation of Nup98 FG domains. | 113 |
| 34575025 | 2021 | NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer. | 89 |
| 39071440 | 2024 | "Off-pore" nucleoporins relocalize heterochromatic breaks through phase separation. | 84 |
| 39475509 | 2024 | NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML. | 83 |
| 34831074 | 2021 | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype. | 81 |
| 33479542 | 2021 | Biomolecular condensation of NUP98 fusion proteins drives leukemogenic gene expression. | 75 |
| 38449868 | 2024 | The nuclear pore protein NUP98 impedes LTR-driven basal gene expression of HIV-1, viral propagation, and infectivity. | 74 |
| 35289742 | 2022 | Nup98-dependent transcriptional memory is established independently of transcription. | 73 |
| 26740045 | 2016 | Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes. | 72 |
| 27031510 | 2016 | Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype. | 70 |
| 38507240 | 2024 | SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport. | 69 |
| 38714656 | 2024 | Impact of distinct FG nucleoporin repeats on Nup98 self-association. | 67 |
| 33097660 | 2020 | SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. | 64 |
| 34163069 | 2021 | Phase separation drives aberrant chromatin looping and cancer development. | 61 |
| 28934014 | 2018 | Nucleoplasmic Nup98 controls gene expression by regulating a DExH/D-box protein. | 61 |
| 25904327 | 2015 | Intranuclear dynamics of the Nup107-160 complex. | 59 |
| 36395068 | 2023 | FLT3ITD drives context-specific changes in cell identity and variable interferon dependence during AML initiation. | 58 |
| 34903620 | 2022 | Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation. | 56 |
| 35258330 | 2022 | Nup98 Is Subverted from Annulate Lamellae by Hepatitis C Virus Core Protein to Foster Viral Assembly. | 56 |
| 23468646 | 2013 | Dynamic association of NUP98 with the human genome. | 55 |
| 37520776 | 2023 | The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML. | 52 |
| 25852164 | 2015 | The transcription factor FoxK participates with Nup98 to regulate antiviral gene expression. | 52 |
| 36789545 | 2023 | Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group. | 51 |
| 32993115 | 2020 | Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia. | 51 |
| 20233715 | 2010 | Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins. | 51 |
| 35217626 | 2022 | A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia. | 49 |
| 30760869 | 2019 | Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia. | 48 |
| 23246429 | 2013 | The role of Nup98 in transcription regulation in healthy and diseased cells. | 48 |
| 33849972 | 2021 | SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98. | 48 |
| 38940430 | 2024 | NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation. | 47 |
| 32344427 | 2020 | CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia. | 47 |
| 37301844 | 2023 | The pediatric leukemia oncoprotein NUP98-KDM5A induces genomic instability that may facilitate malignant transformation. | 46 |
| 36959186 | 2023 | ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias. | 45 |
| 36815378 | 2023 | Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. | 44 |
| 39359452 | 2024 | Prognostic importance of NUP98-rearrangements in acute myeloid leukemia: A systematic review and meta-analysis. | 44 |
| 37353594 | 2023 | NUP98 and RAE1 sustain progenitor function through HDAC-dependent chromatin targeting to escape from nucleolar localization. | 44 |
| 10500183 | 1999 | Autoproteolysis in nucleoporin biogenesis. | 43 |
| 28112737 | 2017 | Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. | 41 |
| 32868895 | 2020 | Covalent inhibition of NSD1 histone methyltransferase. | 40 |
| 39223643 | 2024 | Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia. | 37 |
| 34582559 | 2022 | The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML. | 36 |
| 32620764 | 2020 | Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion. | 36 |
| 35073946 | 2022 | SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation. | 33 |
| 32810969 | 2020 | [Acute myeloid leukemia with co-expression of TEL-ABL1 and NUP98-HOXA9 fusion genes: a case report and literature review]. | 31 |
| 39182032 | 2024 | NUP98::NSD1 and FLT3/ITD co-expression is an independent predictor of poor prognosis in pediatric AML patients. | 25 |
| 34001105 | 2021 | First case report of a NUP98-PMX1 rearrangement in de novo acute myeloid leukemia and literature review. | 25 |
| 23541576 | 2013 | Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking. | 22 |
| 32611575 | 2020 | NUP98 and KMT2A: usually the bride rather than the bridesmaid. | 21 |
| 38536941 | 2024 | Identification of novel NUP98 fusion partners and comutations in acute myeloid leukemia: an adult cohort study. | 21 |
| 32815876 | 2021 | NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML. | 20 |
| 35381677 | 2022 | [A three-series case report and literature review of acute myeloid leukemia with t(7;11)(p15;p15)/NUP98-HOXA9]. | 19 |
| 37147424 | 2023 | NUP98::Nsd1 and FLT3-ITD collaborate to generate acute myeloid leukemia. | 15 |
| 38744828 | 2024 | The landscape of NUP98 rearrangements clinical characteristics and treatment response from 1491 acute leukemia patients. | 15 |
| 29284709 | 2017 | Nup98 regulation of histone methylation promotes normal gene expression and may drive leukemogenesis. | 10 |
| 29928471 | 2018 | p300 suppresses leukemia development in NUP98-HOXD13 driven myelodysplastic syndrome. | 8 |
| 38890447 | 2024 | Combination of menin and kinase inhibitors as an effective treatment for leukemia with NUP98 translocations. | 0 |
| 16105755 | 2005 | NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain proteins. | 0 |
| 27890253 | 2016 | A cryptic translocation leading to NUP98-PHF23 fusion in AML. | 0 |
| 37465857 | 2023 | Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML. | 0 |
| 28392395 | 2017 | Function of Nup98 subtypes and their fusion proteins, Nup98-TopIIβ and Nup98-SETBP1 in nuclear-cytoplasmic transport. | 0 |
| 20545767 | 2010 | Nucleoporin Nup98: a gatekeeper in the eukaryotic kingdoms. | 0 |
| 17442773 | 2007 | NUP98 dysregulation in myeloid leukemogenesis. | 0 |
| 28210005 | 2017 | MLL is essential for NUP98-HOXA9-induced leukemia. | 0 |
| 36351646 | 2022 | [Acute myeloid leukemia harboring NUP98::DDX10]. | 0 |
| 24657637 | 2014 | Nucleoporins and nucleocytoplasmic transport in hematologic malignancies. | 0 |
| 11681408 | 2001 | NUP98 gene fusions in hematologic malignancies. | 0 |
| 35923096 | 2023 | Tau-FG-nucleoporin98 interaction and impaired nucleocytoplasmic transport in Alzheimer's disease. | 0 |
| 37714925 | 2023 | A novel gene fusion RUNX1/ZNF423 promotes leukemic relapse of NUP98-rearranged AML. | 0 |
| 37173550 | 2023 | The Nup98::Nsd1 fusion gene induces CD123 expression in 32D cells. | 0 |
| 15359631 | 2004 | The role of NUP98 gene fusions in hematologic malignancy. | 0 |
| 35187564 | 2022 | Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism. | 0 |
| 37516964 | 2023 | Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure. | 0 |
| 12461755 | 2003 | Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13). | 0 |
| 33479543 | 2021 | Seeking commonalities in fusion proteins of NUP98. | 0 |
| 36911791 | 2022 | Corrigendum: Murine models of acute myeloid leukemia. | 0 |
| 15958703 | 2005 | Hox genes: from leukemia to hematopoietic stem cell expansion. | 0 |
| 39902715 | 2025 | Monitoring measurable residual disease in NUP98::NSD1-positive acute myeloid leukemia. | 0 |
| 17334950 | 2007 | Mitotic regulation of the anaphase-promoting complex. | 0 |
| 39836982 | 2025 | Clinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias. | 0 |
| 20696206 | 2010 | Role of a novel zebrafish nup98 during embryonic development. | 0 |
| 39960447 | 2025 | NUP98-p65 complex regulates DNA repair to maintain glioblastoma stem cells. | 0 |
| 30568173 | 2019 | Dasatinib and navitoclax act synergistically to target NUP98-NSD1(+)/FLT3-ITD(+) acute myeloid leukemia. | 0 |
| 37995102 | 2023 | Acute myeloid leukemia with NUP98::HOXA9 mimicking acute promyelocytic leukemia. | 0 |
| 38318992 | 2024 | Novel ZFPL1::NUP98 fusion gene identified in an adult acute myeloid leukemia patient. | 0 |
| 35167894 | 2022 | Distinct pathologic feature of myeloid neoplasm with t(v;11p15); NUP98 rearrangement. | 0 |
| 23630019 | 2013 | NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia. | 0 |
| 19956199 | 2010 | NUP98-HMGB3: a novel oncogenic fusion. | 0 |
| 36271682 | 2023 | Nizp1 is a specific NUP98-NSD1 functional interactor that regulates NUP98-NSD1-dependent oncogenic programs. | 0 |
| 24371226 | 2014 | NUP98 fusion oncoproteins promote aneuploidy by attenuating the mitotic spindle checkpoint. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12752097 | 2003 | Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001. | Forestier E et al |
| 11165315 | 2001 | Acute leukemia cytogenetics: an evaluation of combining G-band karyotyping with multi-color spectral karyotyping. | Kerndrup GB et al |
| 10502319 | 1999 | 11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome. | Nishiyama M et al |
Summary
Partial GTG-banding karyotype of the t(11;17)(p15;q21).
Citation
Nicolas Duployez ; Stéphanie Struski ; Guillaume Grzych ; Catherine Roche-Lestienne ; Frédérique Payet
t(11;17)(p15;q21) NUP98/?
Atlas Genet Cytogenet Oncol Haematol. 2015-12-01
Online version: http://atlasgeneticsoncology.org/haematological/1233/chromosome-explorer/gene-explorer/meetings/helping-you
