ASXL1
- Known as:
- ASXL1
- Catalog number:
- 002102A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ASXL1
Related genes to: ASXL1
- Gene:
- ASXL1 NIH gene
- Name:
- ASXL transcriptional regulator 1
- Previous symbol:
- -
- Synonyms:
- KIAA0978
- Chromosome:
- 20q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 2002-03-06
- Date modifiied:
- 2019-04-23
Related products to: ASXL1
Related articles to: ASXL1
- Systemic mastocytosis (SM) with associated non-mast cell myeloid neoplasm is a rare condition, defined by the presence of both SM and a clonal non-mast cell neoplasm. Due to its rarity, the demographic and molecular characteristics are poorly understood. This study investigated seven patients diagnosed with this condition at our institution. Our institutional database was searched for "systemic mastocytosis" from 1 January 2020, to 31 December 2025. Each case was annotated to identify the primary cohort of this study, systemic mastocytosis with associated non-mast cell myeloid neoplasm (SM-AHN). Demographic characteristics, outcome, hematologic features at diagnosis, cytogenetics, and molecular characteristics were annotated. Eight cases of isolated SM diagnosed during the same period were also analyzed for comparison. All patients in the database were followed until their death or until 31 December 2025. All data were exported to SPSS v. 28 (IBM, Armonk, NY, USA). A total of seven patients were diagnosed with SM-AHN. Compared to isolated SM, SM-AHN patients showed older age at presentation, poorer hematologic values (increased anemia and thrombocytopenia), higher mutational burden, and poorer outcomes. mutations were most common, predominantly D816V, with other variants like D816Y and L576F also observed. Additional frequent mutations included , , , , , , , and . Our findings, though limited by a small sample size, suggest that SM with associated myeloid neoplasm presents with distinct clinical and molecular features compared to isolated SM. This combined disorder is associated with older age, worse hematologic parameters, a higher mutational burden, and poorer prognosis. The frequent co-occurrence of mutations in other genes, in addition to KIT mutations, highlights the complex molecular landscape. - Source: PubMed
Publication date: 2026/09/17
Seth NehaDeb Pratik Q - Hypoplastic myelodysplastic syndrome (MDS) often overlaps clinically with aplastic anemia and frequently involves clonal hematopoiesis. Thrombopoietin receptor agonists (TPO-RAs), including eltrombopag, are increasingly used to treat cytopenias in hypoplastic marrow failure syndromes; however, their long-term effects on clonal dynamics and marrow fibrosis remain incompletely defined. We report a case of - and -mutated hypoplastic MDS, initially managed as aplastic anemia, in which eltrombopag therapy was associated with a biphasic clinical course. Hematologic parameters initially improved with reduced transfusion requirements; however, prolonged exposure was followed by progressive marrow fibrosis (MF-2 to MF-3), worsening cytopenias, and expansion of a minor paroxysmal nocturnal hemoglobinuria (PNH) clone. Serum lactate dehydrogenase levels increased in parallel with fibrosis progression. After eltrombopag discontinuation, the patient achieved transfusion independence within 3 months and substantial regression of marrow fibrosis, accompanied by recovery of marrow cellularity exceeding the pretreatment baseline. Longitudinal molecular analysis demonstrated modest fluctuations in variant allele frequencies without evidence of overt unidirectional clonal progression. The temporal association between fibrosis progression and hematologic deterioration, together with sustained improvement after drug withdrawal, suggests that eltrombopag may have contributed to treatment-associated microenvironmental remodeling that constrained hematopoiesis after an initial stimulatory phase. This case suggests that eltrombopag-associated marrow fibrosis may be reversible even in the presence of clonal hematopoiesis, and that clinical worsening during TPO-RA therapy does not necessarily indicate irreversible clonal evolution. Careful reassessment of marrow morphology, clonal dynamics, and treatment-related niche perturbation may be warranted in patients with hypoplastic MDS who deteriorate during TPO-RA therapy. - Source: PubMed
Publication date: 2026/09/23
Yoshihara KyokoMatsuda IkuoNannya YasuhitoSamori MamiTomigaki NaruTakahashi SakiOhe ChisatoYoshihara Satoshi - In myelodysplastic neoplasms, autoinflammatory syndromes result from dysregulated innate immunity and cause severe, organ-dominant inflammation. Interleukin-1 signaling through the NLRP3 inflammasome is implicated in the pathogenesis of myelodysplastic disease and related inflammatory complications, especially in the context of RAS-pathway activation. Reports describing therapy-related myelodysplastic syndrome with pulmonary autoinflammatory syndromes are rare, and the efficacy of interleukin-1 blockade in this setting has not been previously documented. A man in his 60s with therapy-related myelodysplastic syndrome (del 5q) following rectal chemoradiation developed a recurrent, lung-predominant autoinflammatory syndrome refractory to corticosteroids and Janus kinase inhibition. Next-generation sequencing identified gain-of-function mutations in NRAS, PTPN11, SF3B1, and ASXL1. On two separate occasions, anakinra produced rapid clinical improvement with normalization of inflammatory biomarkers and radiographic resolution; on both occasions, discontinuation of anakinra led to prompt relapse within days, with ferritin rising to above 5500 ng/mL and C-reactive protein exceeding 300 mg/L. This case demonstrates that interleukin-1-mediated inflammation can drive pulmonary complications in therapy-related myelodysplastic syndrome. Targeted cytokine blockade with anakinra produced reproducible and measurable clinical improvement when conventional therapies were insufficient. The recurrence of symptoms following anakinra withdrawal, and rapid improvement upon re-administration, underscores the functional link between interleukin-1-driven inflammation and clinical outcomes. The RAS/MAPK mutational context and the observed on-off response to anakinra further support an interleukin-1-driven mechanism that merits further investigation. - Source: PubMed
Publication date: 2026/09/20
Smith QuinnArar-Cauley Anna - Mutations in the epigenetic regulator ASXL1 are common in myeloid malignancies and portend a near-universally poor prognosis. While multiple mechanisms for mutant ASXL1-dependent oncogenesis have been proposed, none have been functionally validated in the context of the human hematopoietic stem cell, where these mutations almost certainly arise. Here, we extensively characterized a CRISPR-engineered human hematopoietic stem and progenitor cell model of ASXL1 mutations. In this context, mutant ASXL1 expression decreases differentiation, increases clonogenicity in serial replating experiments, and improves engraftment in immunodeficient mice. We also show that endogenous truncating ASXL1 mutations stabilize the protein and confirm that mutant ASXL1 resists proteasomal degradation. At the transcriptional level, these phenotypes are driven by significant repression of immediate early genes and subtle global transcriptional upregulation, especially of genes repressed during normal differentiation. Using protein-interaction screens, genomic and functional approaches, we link the phenotypic changes in ASXL1-mutant cells to increased chromatin binding of RNAPII, BRD4, and the transcription factor MECOM. The association between ASXL1 and MECOM may reflect a direct or indirect interaction. We also observe aberrant RNA polymerase II pausing dynamics, especially at immediate early genes, in ASXL1-mutated cells. Finally, we demonstrate that ASXL1-mutant AML exhibits increased MECOM activity, consistent with our gene-editing models. Collectively, these studies highlight a highly reproducible model of mutant ASXL1 in the appropriate cell context. Further, they are the first to functionally describe the mutant ASXL1 interactome in the context of human HSCs, identifying MECOM and BRD4 as actionable dependencies with therapeutic potential for ASXL1-mutant myeloid malignancies. - Source: PubMed
Publication date: 2026/09/22
Hall Madison LQuintal AliyaAcharya Sonia NWorme SamanthaNguyen Thai TSchonrock ZacharyTsuchiya MitsuhiroCarlson Hanqian LPacentine Itallia VShrestha Shawn BMacaraeg JommelArmstrong RandallSzczepanski NicoleAdler JamesMcGann JamesEvans-Dutson SaraLusardi Theresa AO'Connell Brendan LAdey Andrew CYardımcı Galip GürkanMaxson Julia EBraun Theodore P - Hepatocellular carcinoma (HCC) remains a global health challenge with high recurrence rates despite surgical resection. Current biomarkers lack sensitivity for early relapse detection, underscoring the need for novel strategies. Circulating tumor DNA (ctDNA) has emerged as a promising tool for minimal residual disease (MRD) monitoring, yet its prognostic and therapeutic implications in HCC remain underexplored. - Source: PubMed
Publication date: 2026/09/20
Xu JianliangWang HuiXu MingxingLi YanjieZhang YiTan JiehuiLin Nan