Ask about this productRelated genes to: NUP98 Blocking Peptide
- Gene:
- NUP98 NIH gene
- Name:
- nucleoporin 98
- Previous symbol:
- -
- Synonyms:
- NUP96
- Chromosome:
- 11p15.4
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-04
- Date modifiied:
- 2016-10-05
Related products to: NUP98 Blocking Peptide
Related articles to: NUP98 Blocking Peptide
- Nucleoporin 98 (NUP98) rearrangements occur in approximately 2-3% of myeloid neoplasms and involve more than 40 partner genes. In acute myeloid leukemia (AML), they define distinct entities associated with adverse prognosis, high rates of chemoresistance, and frequent relapse even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report two patients with therapy-related NUP98-rearranged AML carrying the rare NUP98::TOP1 fusion that occurred after treatment for relapsed/refractory lymphoma. Both patients received CPX-351 as induction therapy and proceeded to allo-HSCT with persistent disease, with approximately 5-10% residual bone marrow blasts. The transplant strategy consisted of an irradiation-based allo-HSCT platform combining total marrow/lymphoid irradiation (TMLI, 20 Gy) with adoptive transfer of regulatory and conventional T cells (Treg/Tcon), administered in the absence of post-transplant pharmacologic immunosuppression to preserve graft-versus-leukemia (GvL) activity while controlling graft-versus-host disease (GvHD). Both patients achieved sustained long-term remission and are alive at 69 and 55 months after allo-HSCT, respectively, without significant transplant-related complications. While no conclusions on treatment efficacy can be drawn from this limited case series, these observations document durable remission despite the active disease at transplant in an ultra-high-risk setting and support further investigation of immune-based transplant strategies in NUP98-rearranged AML. - Source: PubMed
Publication date: 2026/05/23
Cimino GaetanoSembenico RebeccaZorutti FrancescoSaldi SimonettaCaridi MatteoCardinali ValeriaSciabolacci SofiaCrescenzi BarbaraMatteucci CaterinaLa Starza RobertaPucciarini AlessandraZei TizianaIacucci Ostini RobertaAristei CynthiaCarotti AlessandraMecucci CristinaRuggeri LoredanaMartelli Maria PaolaPierini Antonio - Approximately half of newly diagnosed acute myeloid leukemia (AML) cases are cytogenetically normal (CN) when analyzed with conventional karyotyping. However, CN-AML exhibits a wide range of clinical heterogeneity, which may partly be explained by structural variants (SVs) that are not detected with current standard cytogenetic techniques. Here, 48 CN-AML cases were analyzed using optical genome mapping (OGM) for comprehensive SV assessment and to identify novel candidate gene alterations. Abnormalities were detected in 22 of 48 cases (46%). Large SVs, or those affecting leukemia-associated genes, were identified in 16 cases (33%), encompassing 18 abnormalities. Copy-neutral loss-of-heterozygosity regions were detected in seven cases (15%), and they were mutually exclusive with the presence of SVs in all but one case. SVs included eight deletions, six partial tandem duplications, two balanced translocations, and two complex rearrangements. The most frequently altered genes were KMT2A (5 cases) and RUNX1 (3 cases), followed by deletions of NF1 and the 13q14 (DLEU) region (2 cases each). Single alterations included NUP98::NSD1 and deletions of TET2, PRPF8, and FLT3. In addition, as a novel finding, we identified a balanced translocation t(3;20)(p13;q13.12) leading to a putative FOXP1::EYA2 fusion. Notably, the presence of OGM-detected abnormalities was associated with worse disease-specific survival (Mantel-Cox test, p = 0.007). Overall, this study demonstrates that a significant proportion of CN-AML cases harbor clinically relevant SVs, especially those associated with adverse prognosis, that escape detection by standard techniques. Our results support the use of OGM as a streamlined, genome-wide tool for both research and diagnostic applications in AML. - Source: PubMed
Publication date: 2026/05/14
Turtinen TuuniValkama AndrianaWray ChristopherVorimo SandraRäsänen HanneleSavolainen Eeva-RiittaPylkäs KatriMantere Tuomo - We report a large cohort of 95 adult patients with acute myeloid leukemia (AML) harboring NUP98 rearrangements (NUP98r). Patient characteristics included a young age (median 50 years [IQR 38-64]), 20% of therapy-related AML, a high WBC count (median 52×10/L), normal karyotype in 32%, FLT3-ITD in 48% and WT1 mutations in 34%. NUP98::NSD1 fusion was the most common (54%), and these patients were significantly younger (41 y vs. 61 y), had more de novo AML (94% vs. 64%), higher rates of normal karyotypes (56% vs. 4.5%), FLT3-ITD (76% vs. 18%) and WT1 mutations (50% vs. 16%) than other NUP98r AML. The median overall survival (OS) for the entire cohort was 15.2 months (95% CI, 11.9-20.8) and event-free survival was 5.8 months (2-7.5). Among patients treated intensively (n = 73), age (HR = 2.7), FLT3 inhibitor therapy (HR = 0.45) and hematopoietic stem cell transplant (HR = 0.5) influenced OS in univariate analysis. Compared with NUP98 wild-type (WT) AML, NUP98r patients had a prognosis more similar to that of NUP98 WT ELN adverse patients whether initially classified as intermediate (20.3 months [11.7-30.2]) or adverse (15.7 months [13.5-42.9]). However, treatment with FLT3 inhibitors improved prognosis, with median OS not reached and 5-year OS of 53.3%, approaching that of intermediate-risk patients. - Source: PubMed
Publication date: 2026/05/12
Ducourneau BenoitPages ArnaudStruski StéphanieDecamp MatthieuRaffoux EmmanuelBerthon CélineFenwarth LaurèneMarmouset VincentPautas CécileCluzeau ThomasLebon DelphineUzunov MadalinaPereyra PatricioHeiblig MaëlMalfuson Jean-ValèreFarnault LaureDumas Pierre-YvesHieulle JuliaBertoli SarahChantepie SylvainAuger NathalieBidet AudreyMozziconacci Marie-JoelleBoudry AugustinLuquet IsabelleChat LaureenLoyaux RomainEl-Mur LinaClappier EmmanuelleGardin ClaudeHunault MathildeDe Botton StéphanePigneux ArnaudPenther DominiqueDelabesse EricItzykson RaphaelPreudhomme ClaudeDombret HervéRecher ChristianDuployez NicolasMicol Jean-Baptiste - While previous studies have indicated that H3K36me3, which is mediated by Setd2, may regulate the cell fate of mesenchymal stem cells (MSCs) both in vitro and in vivo, the specific role of MSCs in the onset and progression of MDS remains unclear. Thus, the histone methyltransferase Setd2 is implicated in MDS-associated leukemia. This study utilized NUP98-HOXD13 (NHD13) mice with targeted deletion of Setd2 in MSCs. Here, we found that Setd2-deficient mice undergo faster leukemia transformation than control mice do, as evidenced by the abnormal differentiation of hematopoietic stem progenitor cells in the bone marrow, abnormal hematopoiesis, and increased number of blast cells. Compared with that of control mice, the morphology of NHD13 mouse MSCs with Setd2 deficiency was irregular, and the support function of hematopoietic cells was compromised. This study demonstrated that targeted deletion of Setd2 in MSCs facilitates the advancement of MDS. Furthermore, we identified increased expression of coagulation factor XII as a key leukemic transformation mediator in Setd2-deficient MSCs. Moreover, we found that SETD2 expression is significantly lower in high-risk MDS patients than in low-risk MDS patients, further suggesting that the targeted deletion of Setd2 in MSCs is associated with MDS progression. Collectively, our results suggest that Setd2 in MSCs suppresses MDS progression to leukemia through coagulation factor XII-mediated suppression of the stem cell support capacity of MSCs. Overall, this study sheds light on the pathogenesis of MDS and provides a therapeutic strategy for regulating the microenvironment in patients with MDS who cannot be cured by haematopoietic stem cell transplantation. - Source: PubMed
Publication date: 2026/04/30
Wang Rou-JiaLi Zi-JuanChen Bing-YiGuo JuanTao YingLi Hong-PingFei Ming-YueChang Bin-HeZhao Mu-YingShi LeiZhao Si-DaZhang ZhengSu Ji-YingSong Lu-XiHe QiWu DongWu Ling-YunZhang Jia-YingZong Li-JuanSun Xiao-JianZhao You-ShanWang LanChang Chun-Kang - Not available. - Source: PubMed
Publication date: 2026/04/30
Khan AzeemXu JieThakral BeenuToruner Gokce AltayMedeiros L JeffreyQiu Lianqun