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BIOMARKER:

WT1 mutation

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Other names: WT1, WT1 Transcription Factor, Wilms Tumor Protein, Wilms Tumor 1, WT33, NPHS4, WIT-2, AWT1, WAGR, GUD
Entrez ID:
7d
Mutation order in acute myeloid leukemia identifies uncommon patterns of evolution and illuminates phenotypic heterogeneity. (PubMed, Leukemia)
Some mutation orderings had a worse prognosis, but this was mediated by unfavorable mutations, not mutation order. These findings add a dimension to the mutation landscape of AML, identifying uncommon patterns of leukemogenesis and shedding light on heterogeneous phenotypes.
Journal
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NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
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WT1 mutation
18d
UBTF tandem duplications in pediatric myelodysplastic syndrome and acute myeloid leukemia: implications for clinical screening and diagnosis. (PubMed, Haematologica)
Lastly, we report rare duplications within exon 9 of UBTF that phenocopy exon 13 duplications, expanding the spectrum of UBTF alterations in pediatric myeloid tumors. Collectively, we comprehensively characterize pediatric AML and MDS with UBTF-TD and highlight key clinical and pathologic features that distinguish this new entity from other molecular subtypes of AML.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • WT1 (WT1 Transcription Factor)
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WT1 mutation
19d
GATA2 mutant variant allele frequency may reflect prognosis in Chinese adult patients with de novo cytogenetically normal acute myeloid leukemia. (PubMed, Biomol Biomed)
In the intermediate-risk group, the high median VAF of GATA2 (≥38.51%) had no significant effect in OS and RFS compared with the low median VAF (<38.51%). This study offers new insights on the prognosis of GATA2mut in the favorable-risk group, where VAF can be used as a guide.
Journal
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WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • GATA2 (GATA Binding Protein 2)
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CEBPA mutation • WT1 mutation • GATA2 mutation
1m
WT1-related disorders: more than Denys-Drash syndrome. (PubMed, Pediatr Nephrol)
In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations.
Journal
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WT1 (WT1 Transcription Factor)
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WT1 mutation
2ms
Prognostic Impact of Co-occurring Mutations in FLT3-ITD Pediatric Acute Myeloid Leukemia. (PubMed, Blood Adv)
However, ITDpos/NUP98::NSD1 patients continued to have poor outcomes with intensified therapy, including sorafenib. Co-occurring mutational profile in ITDpos AML has significant prognostic impacts is critical to determining risk stratification and therapeutic allocation for ITDpos patients.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)
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FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • CEBPA mutation • WT1 mutation
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sorafenib
2ms
Enrollment closed
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FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
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FLT3-ITD mutation • WT1 mutation • MLL fusion • NUP98-NSD1 fusion
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cyclophosphamide • Blincyto (blinatumomab) • melphalan • fludarabine IV • thiotepa • Neupogen (filgrastim)
2ms
Journal
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WT1 (WT1 Transcription Factor) • GATA2 (GATA Binding Protein 2)
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WT1 mutation
3ms
Impact of Wilms Tumor (WT1) Mutation on Relapse and Overall Survival in Acute Myeloid Leukemia Patients Following Allogenic Stem Cell Transplantation (TCT-ASTCT-CIBMTR 2024)
Despite the younger age and diploid cytogenetics, WT1mut AML patients had comparable OS, RI and NRM to TP53mut AML. WT1mut should be considered high-risk feature in AML patients undergoing alloSCT. Approaches targeting WT1 are urgently needed to improve survival in this population.
Clinical
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WT1 (WT1 Transcription Factor)
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TP53 mutation • WT1 mutation
3ms
Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world. (PubMed, Cancer Med)
Prognosis of CBF-AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo-HSCT may benefit low-risk t(8;21), but further research is needed for conclusive evidence.
Journal • Real-world evidence • Real-world
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WT1 (WT1 Transcription Factor)
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WT1 mutation
4ms
Clinical significance of WT1 in the evaluation of therapeutic effect and prognosis of non-M3 acute myeloid leukemia. (PubMed, Cancer Biol Ther)
Idarubicin + Cytarabine (IA) regimen could reduce the expression level of WT1 after treatment, and Allo-HSCT played an important role in improving the prognosis of patients with WT1 high expression and patients with WT1 negativity. Different clinical background should be taken into consideration when we judge the prognosis and therapeutic effect of patients with WT1 mutations. In addition, WT1 may be an optional MRD marker, which needs regular monitoring.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
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FLT3-ITD mutation • NPM1 mutation • WT1 mutation • WT1 overexpression
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cytarabine • idarubicin hydrochloride
4ms
Clinical Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation Using Busulfan/Cyclophosphamide and Melphalan or Thiotepa As Conditioning Regimen in 37 Patients with Acute Megakaryoblastic Leukemia (ASH 2023)
The conditioning regimens administered were modified Bu/Cy (fludarabine 30 mg/m 2/d×5d; cytarabine 2g/m 2/d×5d; Bu 3...8g/m 2/d×2d; etoposide 100mg/m 2/d×2d; antithymocyte globulin 1...Cyclosporine A (CSA)+ mycophenolate mofetil (MMF)+ short methotrexate (sMTX) were used as graft-versus-host disease (GVHD) prophylaxis...Therefore, it is strongly recommended that allo-HSCT is performed in CR status. However, to corroborate these findings, it is essential to conduct long-term, large-scale clinical research across multiple centers.
Clinical • Clinical data
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NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CD34 (CD34 molecule) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GATA1 (GATA Binding Protein 1) • GLIS2 (GLIS Family Zinc Finger 2) • KDM5A (Lysine Demethylase 5A)
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WT1 mutation
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cytarabine • cyclophosphamide • etoposide IV • methotrexate • melphalan • fludarabine IV • thiotepa • busulfan • cyclosporin A microemulsion
4ms
NGS Profile and the Mathematical Prediction Model for Venetoclax Combination Therapy in HM-Screen-Japan 02 Study (ASH 2023)
Introduction Azacitidine and venetoclax combination therapy (Aza/Ven) is a novel strategy for acute myeloid leukemia (AML). Our mathematical model, involving gene mutations and WT1, could efficiently predict the response of Aza/Ven, which may support the selection of 1 st line treatment. In conclusion, our study revealed the genetic landscape of real-world Aza/Ven therapy and provided a potential prognostic model.
Combination therapy • Next-generation sequencing
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • IDH2 mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • STAG2 mutation • WT1 mutation • ZRSR2 mutation
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Venclexta (venetoclax) • azacitidine
4ms
XPO2 Is Essential for a Subset of AML Cells and Is a Biomarker for Poor Response and Survival in Pediatric and AYA AML (ASH 2023)
XPO2 may function to enhance ribosomal biogenesis, demonstrating a critical role in leukemogenesis. Thus, this work demonstrates a new dependency of pediatric AML on XPO2 highlighting a new target and biomarker for this disease.
Clinical • IO biomarker
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WT1 (WT1 Transcription Factor)
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WT1 mutation
4ms
Preclinical Evaluation of Bisantrene As Single Agent and in Combination with Decitabine for Acute Myeloid Leukemia (ASH 2023)
Anthracyclines, particularly doxorubicin and idarubicin, together with cytarabine, have comprised standard of care induction chemotherapy in acute myeloid leukemia (AML) for almost 4 decades...Hypomethylating agents (HMA; azacytidine, decitabine) provide a less toxic alternative and have improved treatment options for the unfit...Approaches that reduce the toxicity of induction therapy and improve the efficacy of HMA treatment are emerging, e. g. combinations with Venetoclax...These data support that addition of bisantrene to HMA backbone therapy may provide an important new treatment strategy in AML. A prospective Phase Ib/II trial is being planned to evaluate this new therapeutic approach.
Preclinical • Combination therapy
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KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
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KRAS mutation • FLT3-ITD mutation • NPM1 mutation • WT1 mutation
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Venclexta (venetoclax) • cytarabine • doxorubicin hydrochloride • azacitidine • decitabine • idarubicin hydrochloride • Zantrene (bisantrene)
4ms
Persistence of UBTF tandem duplications in remission in acute myeloid leukaemia. (PubMed, EJHaem)
The role of UBTF-TDs in leukemogenesis is yet to be elucidated; however they have been proposed as early initiating events, making them attractive for assessment of MRD and a potential therapeutic target. We present two cases where the UBTF-TD was observed in remission and discuss the implications of these findings in the clinicobiological understanding of this emerging entity.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • WT1 (WT1 Transcription Factor)
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WT1 mutation
4ms
Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG). (PubMed, Leukemia)
In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients' sex in analyses of AML biology and prognostication.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
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FLT3-ITD mutation • NPM1 mutation • KIT mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • WT1 mutation
4ms
Journal
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WT1 (WT1 Transcription Factor)
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WT1 mutation
4ms
Features of the TCR repertoire associate with patients' clinical and molecular characteristics in acute myeloid leukemia. (PubMed, Front Immunol)
The utilization of RNA-seq data enables identification of highly abundant TCRs and correlating these clones with patients' clinical and molecular characteristics. This study further supports the value of high-resolution TCR-Seq analyses to characterize the TCR repertoire in patients.
Journal • IO biomarker
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LAG3 (Lymphocyte Activating 3) • WT1 (WT1 Transcription Factor) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • IL2RA (Interleukin 2 receptor, alpha) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD69 (CD69 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9) • FOXP3 (Forkhead Box P3) • TRB (T Cell Receptor Beta Locus)
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LAG3 expression • WT1 mutation • FOXP3 expression
5ms
Wilms Tumor Gene 1: Lessons from Kidney Development and Cancer. (PubMed, Am J Physiol Renal Physiol)
Yet none of these observations provide a complete picture of Wilms tumor pathogenesis. It appears that the WT1 odyssey is unfinished and still holds a great deal of untilled ground to be explored.
Review • Journal
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WT1 (WT1 Transcription Factor)
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WT1 mutation
5ms
TL-895, a Highly Selective, Covalent Inhibitor of Bruton's Tyrosine Kinase (BTK), Sensitizes Myeloproliferative Neoplasm (MPN)-Blast Phase Stem Cells to Navtemadlin By Targeting Intrinsic Dysregulated MDM2/p53 and NF-Κb Pathways and Disrupting the Protective Tumor Microenvironment (TME) (ASH 2023)
Our results indicate that BTKi therapy might increase susceptibility of MPN-BP SC to MDM2i therapy, by upregulating p53 activity and dampening NF-κB signaling, and also by disrupting protective TME interactions that sustain MPN-BP SC. This novel combination merits further clinical investigation in advanced phase MPN.
IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • MDM2 (E3 ubiquitin protein ligase) • ETV6 (ETS Variant Transcription Factor 6) • BCL2L1 (BCL2-like 1) • WT1 (WT1 Transcription Factor) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DDB2 (Damage Specific DNA Binding Protein 2) • ATF3 (Activating Transcription Factor 3) • BTG2 (BTG Anti-Proliferation Factor 2)
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KRAS mutation • TP53 wild-type • WT1 mutation • ETV6 mutation
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navtemadlin (KRT-232) • M7583
5ms
Influence of Co-Mutational Patterns in Disease Phenotype and Clinical Outcomes of Chronic Myelomonocytic Leukemia (ASH 2023)
These data suggest that somatic mutations in CMML have unique patterns of clustering that define disease phenotype and influence disease outcomes.
Clinical • Clinical data
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • BCORL1 (BCL6 Corepressor Like 1)
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TP53 mutation • BRAF mutation • NRAS mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • CBL mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • WT1 mutation • Chr del(7q) • ETV6 mutation
5ms
Childhood AML Combined with AML1-ETO Fusion Gene and c-KIT or Other Mutations Had Favorable Survival Treated By the C-Huanan AML 2015 Protocol: Study in Multicenter of South of China (ASH 2023)
Combination of c-KIT or FLT3-ITD or ASXL1 or WT1 or NRAS gene mutations with AML1-ETO fusion gene in Childhood AML treated by the C-HUANAN AML protocol did not affected patients'survival.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ASXL1 (ASXL Transcriptional Regulator 1) • WT1 (WT1 Transcription Factor)
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NRAS mutation • FLT3-ITD mutation • KIT mutation • ASXL1 mutation • WT1 mutation • ASXL1 mutation + NRAS mutation
5ms
Ubtf- Tandem Duplications Are Recurrent Somatic Genetic Events in Adult AML and Associate with Additional Structural Variants and a Distinct Gene Expression Profile (Alliance) (ASH 2023)
Our results highlight a susceptibility of those pts to the acquisition of structural variants and suggest a distinct associated biology, with upregulation of ALDH1A3 as possible contributing resistance mechanism. Support: U10CA180821, U10CA180882, U24CA196171; Clinicaltrials.gov Identifiers: NCT00048958 (CALGB 8461), NCT00899223 (CALGB 9665), NCT00900224 (CALGB 20202); https://acknowledgments.alliancefound.org
Clinical • Tumor mutational burden • Gene Expression Profile • Gene expression profiling
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TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ALDH1A3 (Aldehyde Dehydrogenase 1 Family Member A3) • PTPRN (Protein Tyrosine Phosphatase Receptor Type N)
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FLT3-ITD mutation • WT1 mutation
5ms
Characteristics of FLT3-ITD and Efficacy of Sorafenib Treatment in Pediatric AML: A Report from AML-BFM Study Group (ASH 2023)
Conclusions Our preliminary analysis implicates that although addition of sorafenib to the intensive chemotherapy of children and adolescence with FLT3-ITD positive AML, did not improve the survival outcomes in all patients; specific genetic subgroups might benefit from this treatment. These results must be validated in bigger cohorts of patients with longer follow-ups.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)
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FLT3-ITD mutation • WT1 mutation • NSD1 mutation
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sorafenib
5ms
Clinical and Prognostic Implications of WT1 Mutations in De Novo and Relapsed Acute Myeloid Leukemia (ASH 2023)
68% of ND pts received intensive chemotherapy (+/- venetoclax (VEN)) at time of diagnosis with mOS of 26.5 mos vs. 11.1 mos (p = <0.0001) for pts treated with lower intensity therapy (+/- VEN)...Our data suggests that pts with WT1m AML benefit from high intensity induction regimens and SCT at CR1 should be considered in all WT1m pts with ELN2022 intermediate or adverse risk disease. WT1 mutations should also be considered for inclusion into ELN risk stratification given poor overall survival without SCT.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
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FLT3 mutation • NPM1 mutation • WT1 mutation
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Venclexta (venetoclax)
5ms
UBTF Tandem Duplications in Pediatric MDS and AML: Implications for Clinical Screening and Diagnosis (ASH 2023)
We have also expanded the spectrum of UBTFalterations in myeloid neoplasms through the identification of rare UBTF­ duplications in exon 9 that induce a similar transcriptional signature to exon 13 UBTF-TDs. The recent identification of UBTF-TDs in adult and pediatric high-risk myeloid neoplasms has highlighted the importance of understanding and appropriately diagnosing tumors with this genomic alteration, including a new class of alterations that will not be detected by PCR-based screening strategies that specifically target exon 13 of UBTF.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • CD123 (Interleukin 3 Receptor Subunit Alpha) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CD34 (CD34 molecule) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • GATA2 (GATA Binding Protein 2) • CD7 (CD7 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ITGAX (Integrin Subunit Alpha X) • HOXB9 (Homeobox B9)
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FLT3-ITD mutation • NPM1 mutation • KIT expression • WT1 mutation
5ms
Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)
1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.
Clinical
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ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
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DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation
5ms
Decitabine Combined with Low-Dose Chemotherapy Is Effective in the Treatment of Pediatric Refractory/Relapsed Acute Myeloid Leukemia (ASH 2023)
All patients received decitabine 20 mg/ (m2·d) ×5 days, intravenous; combined with idarubicin 5 mg/ (m2·d), qod×3 times, intravenous; cytarabine 10 mg/ (m2·d), q12h×10 days, subcutaneous; granulocyte stimulating factor 5μg/ (kg·d), qd×10 days, intravenous. Decitabine combined with low-dose chemotherapy is a favorable benefit-risk profile and may be a promising option for refractory/relapsed AML in children. Hematopoietic stem cell transplantation after remission can improve survival rate.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CBFB (Core-Binding Factor Subunit Beta 2)
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WT1 mutation
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cytarabine • decitabine • idarubicin hydrochloride
5ms
Cytokine and Mutation Profiling Reveal Patterns of Complete Remission Rates with Lenzilumab Combination Therapy in Chronic Myelomonocytic Leukemia (ASH 2023)
Introduction: Chronic myelomonocytic leukemia (CMML) is characterized by accumulation of classical CD14+CD16- inflammatory monocytes driven in part by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory cytokine. CMML is a disorder of profound innate immune activation, driven by GM-CSF and other pro-inflammatory cytokines. Early treatment with LENZ/AZA, a precision immunotherapeutic approach, leads to a) efficacy in INNATE-1 that exceeds historical CR rates for hypomethylating agents1,2; and b) evolving efficacy in INNATE-2, in which pro-inflammatory activity is more robust. Xu Y, Guo R, Miao M, Zhang G, Lan J, Jin J. Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study.
Clinical • Combination therapy • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • CD14 (CD14 Molecule) • CSF2 (Colony stimulating factor 2) • PHF6 (PHD Finger Protein 6) • IL17A (Interleukin 17A) • CX3CL1 (C-X3-C Motif Chemokine Ligand 1) • IL1B (Interleukin 1, beta) • CRP (C-reactive protein)
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KRAS mutation • RAS mutation • CBL mutation • SRSF2 mutation • WT1 mutation • PHF6 mutation
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azacitidine • LENZ (lenzilumab)
5ms
Characterization of the Molecular Landscape of Pediatric Acute Myeloid Leukemia: A Retrospective AIEOP AML2013/01 Study (ASH 2023)
Overall, in the prospective AIEOP AML2013/01 trial, we described the frequency of different molecular lesions and improved the genetic landscape of AML. The future use of NGS-based screenings could further optimize the characterization of the genetic landscape of childhood AML, thus refining the risk class patients stratification and modulation of treatment approaches.
Retrospective data
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FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • FUS (FUS RNA Binding Protein) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • RBM15 (RNA Binding Motif Protein 15)
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FLT3-ITD mutation • NPM1 mutation • KIT mutation • CEBPA mutation • WT1 mutation • FLT3‐ITD  + NPM1 mutation • MLL fusion
5ms
A Pediatric Patient with Proteinuria and Hepatic Steatosis (KIDNEY WEEK 2023)
With regards to proteinuria and progression to ESRD, therapy is mainly limited in pediatrics to ACEI and ARB. In this patient with an HNF1A associated risk of metabolic syndrome, we consider the role of an SGLT-2 inhibitor for its nephroprotective and antiproteinuric effects.
Clinical
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WT1 (WT1 Transcription Factor) • HNF1A (HNF1 Homeobox A)
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WT1 mutation
6ms
Sorafenib combined with donor-lymphocyte infusions induced long-term unmaintained molecular remission in a patient with primary refractory FLT3-ITD mutated AML after allo-HSCT: 14-year follow-up (DGHO 2023)
Sorafenib and DLIs can induce long-lasting molecular remissions in pts with FLT3-ITD mutations relapsing after HSCT. We speculate that mutated WT1 may have contributed to the exceptional response to this combined treatment.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1) • WT1 (WT1 Transcription Factor) • IL15 (Interleukin 15)
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FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • WT1 mutation
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sorafenib
6ms
UBTF Tandem Duplications are Rare but Recurrent Alterations in Adult AML and Associated with Younger Age, Myelodysplasia and Inferior Outcome (DGHO 2023)
However, in patients under 50 years of age, who represent the majority of UBTF -mutant patients, UBTF -TDs were an independent prognostic factor for inferior event-free (EFS), relapse-free (RFS) and overall survival (OS), which was confirmed by multivariable analyses including established risk factors such as age and ELN2022 genetic risk groups (EFS &lsqb;HR: 2.20; 95% CI 1.52-3.17, p<.001], RFS &lsqb;HR: 1.59; 95% CI 1.02-2.46, p=.039] and OS &lsqb;HR: 1.64; 95% CI 1.08-2.49, p=.020]). In summary, UBTF -TDs appear to represent a novel class defining lesion not only in pediatric AML but also younger adults and are associated with myelodysplasia and inferior outcome in these patients.
Clinical
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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NPM1 mutation • CEBPA mutation • WT1 mutation
6ms
Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia-Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022. (PubMed, Cancers (Basel))
It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)
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NPM1 mutation • WT1 mutation
6ms
Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML. (PubMed, Eur J Haematol)
Detecting NUP98::NSD1 in adult FLT3-ITD-positive AML is crucial to recognizing chemotherapy-resistant group.
Retrospective data • Journal
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FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)
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FLT3-ITD mutation • NPM1 mutation • WT1 mutation
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cytarabine • Xospata (gilteritinib)