News - NPM1 mutation - LARVOL VERI

18h

Functions of the native NPM1 protein and its leukemic mutant. (PubMed, Leukemia)

The NPM1 mutant undergoes changes at the C-terminus of the protein that leads to its delocalization in the cytoplasm of the leukemic cells. Here, we focus also on its biological functions discussing the murine models of NPM1 mutations and the various mechanisms that occur at cytoplasmic and nuclear levels to promote and maintain NPM1-mutated AML.

18 hours ago

Review • Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

The high-risk model associated with SYTL4 predicts poor prognosis and correlates with immune infiltration in AML. (PubMed, Biochem Biophys Rep)

Patients in the high-risk group for these factors experienced significantly poor outcomes, which were closely associated with aDC, CD8 T cells, and TH17 cells. In summary, SYTL4 overexpression is linked to poor prognosis and immune infiltration in AML, with the constructed risk model intended as a prognostic evaluation tool for AML patients.

1 day ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • CD8 (cluster of differentiation 8) • HOXA10 (Homeobox A10)

NPM1 mutation

Classification and Prognostic Stratification Based on Genomic Features in Myelodysplastic and Myeloproliferative Neoplasm- and Their Overlapping Conditions. (PubMed, Cancers (Basel))

Improved survival was observed with transplantation in groups DP2, DP7, and DP9. These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.

1 day ago

Journal

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin)

TP53 mutation • NPM1 mutation • SF3B1 mutation • DDX41 mutation • JAK2 mutation • SETBP1 mutation • CALR mutation

11d

Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in acute myeloid leukemia: real-world multicenter analysis in China. (PubMed, Front Med)

To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in AML.

11 days ago

Journal • Real-world evidence • Real-world

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD + DNMT3A mutation

11d

Comprehensive Genomic Profiling (CGP) of Acute Myeloid Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)

Current best practices for the diagnosis, classification, prognostication, and treatment of AML call for the assessment of the presence and absence of numerous genomic alterations. Therefore, in contrast to single-gene or small-panel molecular testing, the F1H platform can simplify such assessment via a CGP approach.

11 days ago

IO biomarker

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • 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) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)

TP53 mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • U2AF1 mutation • CEBPA mutation • MLL mutation • NPM1 W288

FoundationOne® Heme CDx

13d

Advantages of a genomic DNA-based NGS assay for detection of mutant NPM1 measurable residual disease in AML. (PubMed, Blood Adv)

The NGS/DNA threshold of >0.01% after two cycles of induction chemotherapy identifies significantly more AML patients with an increased relapse risk than current RT-qPCR/cDNA assays. The prognostic significance of mNPM1 MRD appears greatest in FLT3-ITD AML patients.

13 days ago

Journal • Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1)

NPM1 mutation

13d

Impact of COVID-19 on the Clinical Characteristics and Outcomes of Patients with Acute Leukaemia: An academic centre experience. (PubMed, Sultan Qaboos Univ Med J)

The complete remission (P = 0.48) and the overall survival rates were similar (P >0.05). Except for an increased rate of acute leukaemia and a lower platelet count, the COVID-19 pandemic did not impact the presentation and outcomes of acute leukaemia.

13 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

NPM1 mutation • FLT3 positive

13d

The Clinical Impact of NPM1 Mutations and the Effect of Concurrent Mutations in Acute Myeloid Leukemia: Unraveling the Prognostic Significance. (PubMed, Health Sci Rep)

The evaluation of NPM1 mut and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.

13 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3‐ITD + DNMT3A mutation

15d

Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia. (PubMed, Ann Hematol)

In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1+FLT3-ITD- AML. Further studies with the large number of patients are warranted.

15 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit)

FLT3-ITD mutation • NPM1 mutation • HIF1A overexpression • HIF1A expression

cytarabine

16d

Influence of Nucleophosmin (NPM1) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration. (PubMed, J Clin Oncol)

The evaluation of specific NPM1 genotypes identified AML patients with type D mutations being significantly associated with inferior outcomes, suggesting a reclassification of D cases to higher-risk groups.

16 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

17d

VINCENT: Venetoclax Plus Azacitidine Versus Intensive Chemotherapy for Fit Patients With Newly Diagnosed NPM1 Mutated AML (clinicaltrials.gov)

P2, N=146, Recruiting, Technische Universität Dresden | Not yet recruiting --> Recruiting

17 days ago

Enrollment open

NPM1 (Nucleophosmin 1) • CD33 (CD33 Molecule)

NPM1 mutation • CD33 positive

Venclexta (venetoclax) • cytarabine • azacitidine • Mylotarg (gemtuzumab ozogamicin)

17d

Molecular leveraging of HOX-embedded non-coding RNAs in the progression of acute myeloid leukemia. (PubMed, Hum Cell)

We discuss how specific HOX ncRNA networks are leveraged by leukemic cells, presenting an opportunity to explore targeted therapies and address the molecular heterogeneity of AML. Additionally, the aberrant expression of HOX ncRNAs such as HOXB derived ncRNAs in NPM1 mutated AML suggests their potential utility as improved biomarkers and for prognostication of patients with specific molecular aberrations.

17 days ago

Review • Journal

NPM1 (Nucleophosmin 1) • HOTAIR (HOX Transcript Antisense RNA) • HOTTIP (HOXA Distal Transcript Antisense RNA) • MIR196B (MicroRNA 196b)

NPM1 mutation

20d

Targeting chromatin modifying complexes in acute myeloid leukemia. (PubMed, Stem Cells Transl Med)

This review explores recent discoveries of how leukemic cells hijack these complexes and their interactions with other chromatin regulators to promote disease progression. We also discuss inhibitors targeting these complexes that have demonstrated therapeutic efficacy in preclinical and clinical studies and propose novel therapeutic combinations targeting the KMT2A and PRC1/2 broader interacting networks to overcome issues of resistance to existing monotherapies.

20 days ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)

NPM1 mutation • MLL rearrangement

20d

Genotype-immunophenotype relationships in NPM1 -mutant AML clonal evolution uncovered by single cell multiomic analysis. (PubMed, bioRxiv)

Analysis of longitudinal samples from patients on therapy identified dynamic clonal, transcriptomic, and immunophenotypic changes. Our studies provide resolved understanding of leukemic clonal evolution and the relationships between genotype and cell state in leukemia biology.

20 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

24d

Immune-based subgroups uncover diverse tumor immunogenicity and implications for prognosis and precision therapy in acute myeloid leukemia. (PubMed, Front Immunol)

Moreover, we observed a positive correlation between sample immune infiltration and sample resistance to elesclomol and panobinostat, whereas a negative correlation was found with venetoclax resistance. Our study enriches the current AML risk stratification and provides guidance for precision medicine in AML.

24 days ago

Journal • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL1RAP (Interleukin 1 Receptor Accessory Protein) • CD96 (CD96 Molecule) • CLEC12A (C-Type Lectin Domain Family 12 Member A)

NPM1 mutation

Venclexta (venetoclax) • Farydak (panobinostat) • elesclomol (STA-4783)

28d

AUGMENT-101: A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (clinicaltrials.gov)

P1/2, N=413, Recruiting, Syndax Pharmaceuticals | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

28 days ago

Trial completion date • Trial primary completion date

KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

NPM1 mutation • MLL rearrangement • MLL rearrangement • NUP98 rearrangement

Revuforj (revumenib) • Tybost (cobicistat)

29d

Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead. (PubMed, J Hematol Oncol)

More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.

29 days ago

Review • Journal • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement

Venclexta (venetoclax) • cytarabine

30d

Longitudinal ultra-sensitive mutation burden sequencing for precise minimal residual disease assessment in AML. (PubMed, Nat Commun)

The ROC area under curve (AUC) is 0.98 when predicting relapse within 30 weeks of CR timepoint 2 (N = 20). Furthermore, we demonstrate quantitating VAF below 0.01% is essential for accurate relapse prediction.

30 days ago

Journal • Tumor mutational burden • Minimal residual disease

TMB (Tumor Mutational Burden) • NPM1 (Nucleophosmin 1)

NPM1 mutation

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2). (PubMed, Int J Mol Sci)

FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.

1 month ago

Clinical • Journal

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • FANCA (FA Complementation Group A)

NPM1 mutation • DNMT3A mutation • FANCA mutation

azacitidine

Molecular measurable residual disease monitoring and transplant indications in NPM1 mutated acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

In this review, we evaluate the prognostic role of MRD monitoring in NPM1 mutated AML and its use as a predictive biomarker to refine risk stratification and inform decision making regarding treatment. We explore the impact of pre-HCT MRD positivity on post-HCT outcomes in this AML subset, and how HCT-related factors such as conditioning intensity may influence this risk.

1 month ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy. (PubMed, Cancer Cell)

We next use a generalizable, reversible approach to demonstrate that mutation reversion results in rapid leukemic regression with distinct differentiation patterns depending upon co-occurring mutations. These studies provide a path to experimentally model sequential mutagenesis, investigate mechanisms of transformation and probe oncogenic dependency in disease evolution.

1 month ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3 mutation • NPM1 mutation • DNMT3A mutation

OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine. (PubMed, World J Surg Oncol)

This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • SRSF2 (Serine and arginine rich splicing factor 2) • GPX4 (Glutathione Peroxidase 4) • CYB5A (Cytochrome B5 Type A) • CPT1A (Carnitine Palmitoyltransferase 1A) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

FLT3-ITD mutation • IDH1 mutation • NPM1 mutation • SRSF2 mutation • NPM1 expression • NPM1 mutation + SRSF2 mutation

Unveiling the Genetic and Clinical Differences of Acute Myeloid Leukemia (AML) in Obese Patients. (PubMed, Eur J Haematol)

The molecular features of obese AML patients significantly differ from non-obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.

1 month ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Target-Capture Next-Generation Sequencing (NGS) for Use in Molecular-Based Research of Myeloid Measurable Residual Disease (MRD) (AMP 2024)

Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.

1 month ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)

FLT3-ITD mutation • NPM1 mutation • FLT3 D835Y • FLT3 D835 • IDH2 R172K • KIT D816V • IDH1 R132C • JAK2 V617F • IDH1 R132 • IDH2 R172

SureSeq™ Myeloid MRD Panel

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

1 month ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Characteristics and Outcome of FLT3-ITD-Positive Acute Myeloid Leukemia. (PubMed, Clin Lab)

Allo-HSCT immediately following complete remission could improve outcomes for young adults diagnosed with FLT3-ITD-positive AML. However, we found no statistical difference in the overall response rate (ORR) and clinical outcome between sorafenib combined with chemotherapy and chemotherapy alone.

1 month ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

sorafenib

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • IDH1 mutation • FLT3 mutation • NPM1 mutation

PEMAZA: MRD-guided Treatment in NPM1mut AML Patients (clinicaltrials.gov)

P2, N=28, Recruiting, Technische Universität Dresden | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Aug 2023 --> Dec 2025

1 month ago

Trial completion date • Trial primary completion date

NPM1 mutation

Keytruda (pembrolizumab) • azacitidine

Development and Validation of a Biopsy-Free Scoring System for Screening Myelodysplastic Syndrome (MDS) and Associated Diseases in Cytopenic Patients (ASH 2024)

For patients with a probability score < 45%, a bone marrow study may not be needed, with a recommended follow-up every 6–12 months. This comprehensive analysis provides a useful and non-invasive predictive model that enhances diagnostic accuracy which potentially reduces unnecessary procedures.

1 month ago

Clinical • Biopsy

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

Oncomine Myeloid Research Assay

Measurable Residual Mutated NPM1 before Allogeneic Transplant for Acute Myeloid Leukemia (ASH 2024)

NPM1 MRD positive patients receiving nonmyeloablative conditioning or reduced-intensity conditioning (RIC) without melphalan (mel) had increased risk of relapse or death compared to patients receiving myeloablative conditioning or RIC with mel, regardless of FLT3-ITD co-mutational status (3yrs : relapse 87% vs 55%, P=0.006; OS 15% vs 42%, P=0.013). Conclusions : In patients with NPM1 mutated AML from the Pre-MEASURE study, we show that detection of residual NPM1 variants in pre-transplant blood during CR1 using a highly sensitive DNA-based assay is associated in a dose-dependent manner with a significantly increased risk of relapse and death after allo-HCT, which can be mitigated in part by conditioning regimen. In patients co-mutated for both FLT3-ITD and NPM1 at diagnosis, NPM1 should be prioritized as a target for NGS-MRD if only one test is available.

1 month ago

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation

FLT3 ITD MRD Assay • NPM1 Mutation Assay

melphalan

Prognostic Role of NGS-Based MRD Assessment in FLT3-TKD Mutated Patients with Acute Myeloid Leukemia (ASH 2024)

Only two patients in the MRD negative group received the FLT3 inhibitor midostaurin combined with chemotherapy...NGS-MRD was not prognostic in this cohort of FLT3-TKD mutated AML patients. Shared first authors : Isabell Arnhardt, Christian M Vonk Shared senior authorship : Michael Heuser, Peter J.M. Valk

1 month ago

Clinical • Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • 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)

FLT3-ITD mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

Prognostic Significance of Low Copy Number FLT3 and NPM1 mrd As Detected By Ultra-Sensitive Next Generation Sequencing (ASH 2024)

While most patients with "low-level" MRD positivity later have negative MRD testing, there is a subset of patients that go on to develop "high-level" MRD and are thus at increased risk of relapse. These data suggest that MRD positivity below the clinically-validated limit of detection is challenging to interpret, and that longitudinal MRD monitoring is vital for disease surveillance.

1 month ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation • FLT3‐ITD + NPM1 mutation

FLT3 ITD MRD Assay • NPM1 Mutation Assay

IDH2 Mutation Is Associated with Favorable Outcome Among Older Adults with Newly Diagnosed Acute Myeloid Leukemia Treated with Lower-Intensity Therapy (ASH 2024)

Among the LIT treated patients, 96 patients received treatment with an IDH inhibitor, and 237 patients received a hypomethylating agent (HMA) plus venetoclax...IDH2MUT was associated with a lower HR of death among patients treated with LIT, which was not seen in patients receiving IC. The high prevalence of IDH mutations suggests that IDH inhibitors used as single agents or in combination with lower-intensity therapies are an important class of drugs for this older patient population as they are generally well tolerated, that need further investigation.

1 month ago

Clinical

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • SRSF2 (Serine and arginine rich splicing factor 2)

IDH2 mutation • NPM1 mutation

FoundationOne® Heme CDx

Venclexta (venetoclax)

Rare Types of NPM1 Mutations Share a Similar Molecular Background to the Common NPM1 Variant and Have No Impact on Survival in Adults with Acute Myeloid Leukemia (ASH 2024)

Conclusion : The rare NPM1 mutation subtypes share a similar pattern of co-mutations with the common NPM1 type A, are similarly affected by the FLT3 status and by the presence of a TM-phenotype and feature similar OS. Publicly available datasets can be exploited to collect information on rare entities which would be otherwise poorly characterized.

1 month ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

NPM1 mutation

MSK-IMPACT Heme

Pre-emptive therapeutic decisions based on measurable residual disease status in acute myeloid leukemia: ready for prime time? (PubMed, Leukemia)

Therefore, preemptive interventions on the natural history of MRD positivity are an active area of research beyond its initial prognostic function. Targeting MRD in AML with innovative treatment strategies can improve patient outcomes.

1 month ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1)

NPM1 mutation

2ms

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics. (PubMed, Asian Pac J Cancer Prev)

This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)

FLT3-ITD mutation • NPM1 mutation • WT1 mutation • FLT3‐ITD + NPM1 mutation • FLT3-ITD mutation + WT1 mutation • FLT3‐ITD + WT1 mutation

2ms

AML-VAC-XS15-01: protocol of a first-in-human clinical trial to evaluate the safety, tolerability and preliminary efficacy of a multi-peptide vaccine based on leukemia stem cell antigens in acute myeloid leukemia patients. (PubMed, Front Oncol)

The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals.

2 months ago

P1 data • Journal • IO biomarker

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)

IDH2 mutation • NPM1 mutation • IDH2 R140Q

2ms

The prognostic significance of genetics in acute myeloid leukemia under venetoclax-based treatment. (PubMed, Ann Hematol)

Its combination with HMA or low-dose cytarabine (LDAC) has been shown to enhance the response rates and prolong the survival outcomes of older or unfit patients with AML. Additionally, we examined the response rates and survival outcomes of CBF-AML when treated with a VEN-based regimen. Moving forward, it is imperative that risk stratification for LIT becomes more nuanced to better align with the requirements of personalized diagnosis and treatment strategies.

2 months ago

Review • Journal • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation

Venclexta (venetoclax) • cytarabine

2ms

Characteristics and Prognosis of "Acute Promyelocytic Leukemia-like" Nucleophosmin-1-Mutated Acute Myeloid Leukemia in a Retrospective Patient Cohort. (PubMed, Biomedicines)

Our findings contribute to a comprehensive characterization of NPM1-mutated AML, enhancing diagnostic accuracy and aiding in the detailed classification of the disease. This information may potentially guide targeted therapies or differentiation-based treatment strategies.

2 months ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule)

FLT3 mutation • NPM1 mutation • DNMT3A mutation • TET2 mutation

2ms

Immunotherapeutic Potential of Mutated NPM1 for the Treatment of Acute Myeloid Leukemia. (PubMed, Cancers (Basel))

Preclinical trials have shown that the use of PD-1/PD-L1 checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with AML NPM1mut may be better suited to immunogenic strategies that are based on the inhibition of the PD-1 immune checkpoint pathway than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PD-1 inhibitors.

2 months ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

NPM1 (Nucleophosmin 1)

NPM1 mutation

2ms

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia. (PubMed, Bone Marrow Transplant)

Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • IDH2 mutation • NPM1 mutation

Idhifa (enasidenib)

2ms

Quizartinib with donor lymphocyte infusion for post-transplant relapse of FLT3-ITD-positive acute myeloid leukemia. (PubMed, Int J Hematol)

The patient achieved hematological CR on day 163 and remained in molecular CR 3 years after allo-HCT without adverse effects. Quizartinib combined with DLI may be a feasible treatment for early relapse of FLT3-ITD-positive AML after allo-HCT, even with concurrent DNMT3A and NPM1 mutations.

2 months ago

Journal • Post-transplantation

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • DNMT3A R882

Vanflyta (quizartinib)