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
- Calreticulin gene (CALR) mutations are seen in 25%-30% of myeloproliferative neoplasms (MPNs). We report outcomes and high-risk genomic signatures in 149 patients with CALR-mutated MPN. CALR-mutated essential thrombocythaemia (n = 106) progressed to myelofibrosis (n = 40) at a median of 20.4 years, and 20-year overall survival (OS) was 81%. In 83 patients with myelofibrosis, the median leukaemia-free survival (LFS) was 12.9 years, and OS was 13.9 years. Median survival after leukaemia transformation was 6.8 months. High molecular risk (HMR) mutations included ASXL1, EZH2, SRSF2, U2AF1 (Q157), IDH1/2, TP53, SETBP1, KRAS, NRAS and RUNX1 (later five not included in Mutation-Enhanced International Prognostic Score System [MIPSS70]-plus v2.0); and were associated with a significantly higher leukaemic transformation, inferior LFS and OS (hazard ratio [HR]: 3.82, 95% confidence interval [CI]: 1.30-11.18); with worst outcomes in patients with ≥2 HMR. Independent of MIPSS70-plus v2.0, TP53, KRAS and RUNX1 mutations adversely impacted LFS and OS (HR: 2.87, 95% CI: 1.20-6.88; HR: 3.80, 95% CI: 1.37-10.54; HR: 5.61, 95% CI: 1.53-20.52 respectively). Patients without HMR had a negligible rate of progression. Overall, outcomes are determined not by CALR 'driver' mutation, but by the somatic mutations that can emerge during disease evolution. Hence, serial molecular profiling is important for risk stratification. HMR, including TP53, KRAS and RUNX1, confer inferior survival and support early transplantation consideration. - Source: PubMed
Publication date: 2026/10/07
Mawalkar ReshamTsai Hua-LingPasca SergiuGondek Lukasz PHalper-Stromberg EitanXian Rena RGocke ChristopherRappazzo Katherine CKarantanos TheodorosSmith B DouglasPrince Gabrielle TDeZern Amy EAmbinder Alexander JGojo IvanaWebster Jonathan ADalton William BrianGhiaur GabrielLevis MarkResar LindaMoliterno Alison RJain Tania - The combination of azacitidine and venetoclax (Aza/Ven) is an effective treatment for acute myeloid leukemia (AML); however, biological factors underlying heterogeneous treatment responses across diverse genetic backgrounds remain incompletely defined. We analyzed 97 AML patients treated with Aza/Ven in the prospective HM-SCREEN-Japan 02 study using targeted next-generation sequencing (NGS) of 53 genes, cytogenetic analyses, and clinical variables. Somatic mutations were categorized into type 1 (FLT3, PTPN11, WT1, IDH1/2, NPM1, NRAS) and type 2 (GATA2, KRAS, TP53, RUNX1, STAG2, ASXL1, ZRSR2, TET2) groups based on a previously proposed framework describing clonal characteristics. Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 53.8%, 52.1%, and 50.0% of patients treated in the first-, second-, and ≥third-line settings, respectively. Among 53 first-line patients with pre-treatment NGS data, type 1-only mutations were more frequently observed in responders (CR/CRi 72%), whereas type 2-only mutations were enriched in non-responders (CR/CRi 33%). In the first-line setting, achievement of CR/CRi following Aza/Ven was associated with improved overall survival. In addition, an exploratory mathematical model integrating baseline clinical variables demonstrated strong discriminatory performance for treatment response, including in cases without established prognostic mutations. In conclusion, Aza/Ven demonstrated consistent clinical activity across treatment lines in this real-world cohort. Mutational patterns classified by a type 1/type 2 framework were associated with differential response patterns in the first-line setting. Integrative modeling approaches may support the interpretation of response heterogeneity, particularly in genetically uninformative AML. - Source: PubMed
Publication date: 2026/10/01
Ueda TomoakiFukushima KentaroChi SunggiHaeno HiroshiYoshimoto GoichiArai HironoriIkeda DaisukeIchikawa MotoshiTakahashi NaotoHosono NaokoYamauchi TakahiroKondo TakeshiKusumoto ShigeruKuroda JunyaMinami Yosuke - Macrophages are major contributors to inflammatory responses in acute kidney injury (AKI) and rapidly alter their gene expression through epigenetic regulation. This study focused on ASXL1, a chromatin modifier regulating histone marks consisting of H3K27me3 (repressive) and H3K4me3 (activating) in M1 macrophages. We found that ASXL1-positive M1 macrophages were significantly increased in the unilateral ischemia-reperfusion injury kidneys of male mice in the acute phase. In cultured M1 macrophages, RNA sequencing revealed that Asxl1 knockdown upregulated inflammatory response genes such as Il6 and Il1b. Conversely, the expression of anti-apoptotic genes Csf3 and Lcn2 was suppressed, and pathways related to interleukin-17 signaling and Fcγ receptor-dependent phagocytosis were downregulated. In co-culture experiments, Asxl1 silencing in M1 macrophages induced more severe apoptosis and reduced proliferation of mouse renal cortical tubular cells. Mechanistically, chromatin immunoprecipitation analysis demonstrated that Asxl1 knockdown significantly decreased H3K27me3 levels at the Il6 and Il1b promoter regions and H3K4me3 levels at the Csf3 and Lcn2 promoter regions in M1 macrophages. These findings indicate that ASXL1 suppresses excessive inflammatory cytokine expression and preserves anti-apoptotic activity through histone modifications, while maintaining phagocytic capacity in M1 macrophages. ASXL1 in M1 macrophages thus attenuates inflammatory activation and macrophage-mediated renal tubular cell damage in AKI. - Source: PubMed
Ogura YoshiyasuSugasawa TakehitoNangaku MasaomiMimura Imari - Five years after the first readout of the ASCEMBL trial, asciminib evidence has rapidly expanded across the chronic myeloid leukemia (CML) treatment landscape. Subsequent studies and growing real-world experience have also clarified its efficacy and tolerability in earlier treatment lines. As the first allosteric inhibitor targeting the BCR::ABL1 myristoyl pocket, asciminib provides a mechanistically distinct approach that may reduce cross-resistance and toxicity associated with ATP-competitive TKIs. At a time when treatment goals in CML emphasize long-term tolerability, quality of life, and the potential for treatment-free remission (TFR), asciminib's unique molecular and clinical profile justify its inclusion in CML treatment considerations. In this expert opinion review, we synthesize emerging clinical and real-world evidence for asciminib and discuss practical considerations for its integration into contemporary CML management, including its potential im-plications for TFR eligibility. We also explore the role of next-generation sequencing in detecting salvageable resistance mutations, the prognostic significance of co-mutations such as ASXL1, and the concept of mutation-guided treatment sequencing. Collectively, these data position asciminib as an established later-line therapy and an emerging frontline option, with the potential to improve long-term treatment sustainability through favorable tolerability and early molecular response kinetics. - Source: PubMed
Publication date: 2026/09/23
Kim Dennis Dong HwanBusque LambertHillis ChristopherLaneuville PierreSavoie Mary Lynn - Clonal monocytosis of undetermined significance (CMUS) and clonal cytopenia with monocytosis of undetermined significance (CCMUS) are recently defined precursor states, with unclear progression rates to myeloid neoplasms (MN), including chronic myelomonocytic leukemia (CMML). We evaluated a cohort of 958 patients with sustained monocytosis ( ≥ 0.5 ×10/L, ≥10%) and stringently excluded MN. Among 958 patients, 74 met criteria for CMUS (n = 10) and CCMUS (n = 64), respectively. These patients were compared with a cohort with oligo monocytic-CMML (OM-CMML; n = 47). CMUS patients were younger (median age: 63 years), whereas CCMUS demonstrated lower BM blast %, in comparison to OM-CMML (median blast %: 1 vs. 2). OM-CMML was enriched for TET2 (60% vs. 32%, p = 0.012), ASXL1 (40% vs. 9%, p < 0.001), and SRSF2 (45% vs. 8%, p < 0.001) mutations, while CMUS/CCMUS had higher rates of DNMT3A (36% vs. 9%, p < 0.001) and PPM1D (12% vs. 0, p = 0.029) mutations. Mutation burden and VAF for most mutations (except SRSF2) were significantly higher in OM-CMML. DNMT3A mutations in CMUS/CCMUS often involved the methyltransferase (MT) domain, and MT domain mutations and co-mutations were associated with progression of CCMUS to CMML. With a median follow-up of 31 months, there were no progression events in CMUS patients, while 13% of CCMUS patients progressed to MN, mainly CMML (7/8). Median OS was inferior in OM-CMML (71 months) compared to CMUS/CCMUS (not reached), p < 0.001. Our findings demonstrate that CMUS and CCMUS represent biologically distinct clonal states with variable progression risk and highlight the importance of integrating morphologic and genomic data to refine classification. - Source: PubMed
Publication date: 2026/09/28
Kewan TariqZureigat HadilPankaj PradeepHe RongJevremovic DraganGreipp PatriciaSaliba Antoine NMatin AasiyaHefazi Torghabeh MehrdadGangat NaseemaHogan WilliamAlkhateeb HassanArana Yi CeciliaForan JamesLitzow MarkShah Mithun VinodBegna KebedeTalha BadarKusne YaelMangaonkar Abhishek AAl-Kali ArefReichard KaarenPatnaik Mrinal M