News - NPM1 mutation - LARVOL VERI

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.

1 day 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.

2 days 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.

2 days 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.

4 days 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.

4 days 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.

4 days 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.

5 days 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.

5 days 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

11d

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.

11 days ago

Retrospective data • Journal

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

FLT3-ITD mutation • NPM1 mutation

sorafenib

12d

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.

12 days 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

12d

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

12 days ago

Trial completion date • Trial primary completion date

NPM1 mutation

Keytruda (pembrolizumab) • azacitidine

12d

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.

12 days 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 • STAG2 mutation

Oncomine Myeloid Research Assay

12d

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

To our knowledge, our study is the first to assess the clinical impact of MRD detected below the clinically-validated limit of detection by ultra-sensitive NGS. Findings from our retrospective study were consistent with previously published data suggesting the presence of “high level” MRD (i.e. above the current clinically-validated limit of detection) is associated with increased risk of AML relapse in both NPM1 and FLT3-ITD mutated AML.

12 days 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

12d

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). 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.

12 days 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

12d

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

12 days 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 • DNMT3A mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

12d

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... A total of 1023 patients with ND AML were identified. Patients had a median age of 72 (range 60-92) years and the majority were non-Hispanic White (83.2%), and male (57.6%). Ninety-nine (9.7%) patients were IDH1MUT, 193 (18.9%) patients were IDH2MUT including 10 (1.0%) patients with a co-occurring IDH1 and IDH2 gene mutations.

12 days 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)

12d

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)

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.

12 days ago

Clinical

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

NPM1 mutation • DNMT3A mutation • FLT3 wild-type

MSK-IMPACT Heme

14d

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.

14 days ago

Review • Journal

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

NPM1 mutation

20d

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.

20 days 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

20d

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.

20 days ago

P1 data • Journal • IO biomarker

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

IDH2 mutation • NPM1 mutation • IDH2 R140Q

20d

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.

20 days 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

23d

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.

23 days 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

23d

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.

23 days ago

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

NPM1 (Nucleophosmin 1)

NPM1 mutation

23d

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.

23 days 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)

23d

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.

23 days 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)

24d

Menin-mll protein-protein interaction inhibitors: a patent review (2021-present). (PubMed, Expert Opin Ther Pat)

Therefore, new drug discovery strategy should be considered in advance. The expert opinion was proposed from several aspects, such as developing diverse chemical structures, discovering covalent inhibitors, designing small molecular PROTACs, and targeting the amino acids mutations for next-generation inhibitors.

24 days ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • KMT2A mutation

27d

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML (clinicaltrials.gov)

P3, N=415, Not yet recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland

27 days ago

New P3 trial • Combination therapy

NPM1 (Nucleophosmin 1)

NPM1 mutation

Venclexta (venetoclax) • azacitidine • Revuforj (revumenib)

28d

Acute myeloid leukemia with NPM1, IDH2, and SETD2 mutations mimicking acute promyelocytic leukemia: A case report and literature review. (PubMed, Medicine (Baltimore))

The comprehensive evaluation of bone marrow morphology, immunology, cytogenetics, and molecular biology is essential for the accurate diagnosis of acute myeloid leukemia.

28 days ago

Review • Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

NPM1 mutation • SETD2 mutation

Venclexta (venetoclax) • azacitidine

Erratum for the Research Article: "Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia" by D. Sakthivel et al. (PubMed, Sci Adv)

No abstract available

1 month ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Prognostic impact of clonal hematopoiesis mutations at complete molecular remission in acute myeloid leukemia with NPM1 mutation. (PubMed, J Cancer Res Clin Oncol)

There was no significant difference in event-free survival (EFS) or overall survival (OS) between the patients with and without CH-mutations at CMR or between the patients without allogeneic hematopoietic stem cell transplantation (allo-HSCT) of the two groups. In conclusion, our results suggested that CH-mutations probably did not have prognostic significance in patients with NPM1c AML who achieved CMR, and may be inappropriately for MRD monitoring.

1 month ago

Retrospective data • Journal

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

NPM1 mutation • DNMT3A mutation • TET2 mutation

Mutant NPM1 marginally impacts ribosome footprint in acute myeloid leukemia cells. (PubMed, EJHaem)

In contrast, Ribo-seq data showed negligible changes in the ribosome footprint in both cell lines, implying that the presence of NPM1c does not influence ribosome abundance and positioning on mRNA. While it is predictable that NPM1c exerts its leukemogenic activity at multiple levels, ribosome footprint does not seem influenced by the presence of mutant NPM1.

1 month ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation • NPM1 expression

Spontaneous remission of acute myeloid leukemia with NPM1 mutation during pregnancy:a case report (PubMed, Zhonghua Xue Ye Xue Za Zhi)

No abstract available

1 month ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Targeting the Tumour Antigen 5T4 using CAR-T Cells for the Treatment of Acute Myeloid Leukaemia. (PubMed, Mol Cancer Ther)

A murine model for AML demonstrated that CAR-T cells recognise and kill in vivo 5T4-expressing tumour cells. These results highlight 5T4 as a promising target for immune intervention in AML and that CAR-T cells can be considered a powerful personalised therapeutic approach to treat AML.

1 month ago

Journal • CAR T-Cell Therapy • IO biomarker

NPM1 (Nucleophosmin 1) • TPBG (Trophoblast Glycoprotein)

NPM1 mutation • TPBG expression

Integrating holotomography and deep learning for rapid detection of NPM1 mutations in AML. (PubMed, Sci Rep)

This study demonstrates the potential of HT combined with deep learning for early, efficient, and cost-effective diagnosis of AML, offering a promising alternative to traditional stepwise genetic testing methods and providing additional assistance in morphological myeloblast discrimination. This approach may revolutionize the diagnostic process in leukemia, facilitating early detection and potentially reducing the reliance on extensive genetic testing.

1 month ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

AML typical mutations (CEBPA, FLT3, and NPM1) identify a high-risk CMML independent of CPSS-Mol classification. (PubMed, Blood Adv)

The genetic profile of these mutCFN CMML patients closely resembled that of AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible, and consider certain targeted therapies approved for use in AML.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

IDH1 mutation • IDH2 mutation • FLT3 mutation • NPM1 mutation • CEBPA mutation

Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia. (PubMed, Nat Genet)

Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction.

1 month ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)

NRAS mutation • IDH2 mutation • NPM1 mutation

Design and development of a series of 4-(piperazin-1-yl)pyrimidines as irreversible menin inhibitors. (PubMed, Eur J Med Chem)

This effect of 37 is not involved in proteasomal degradation, and may directly affect the synthesis of menin protein, which offers a significant advantage in addressing acquired resistance to menin inhibitors. Further study showed that compound 37 has prolonged anti-leukemic action and exhibits promising in vivo efficacy, making it a valuable probe for further menin-MLL interaction studies.

1 month ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • MLL rearrangement • MLL rearrangement • MLL fusion

2ms

AMLM26/T3 INTERCEPT: A multi-arm trial for patients with acute myeloid leukaemia investigating new treatments which target early relapse and changes in disease characteristics - Low-dose cytarabine (LDAC) + Venetoclax (ACTRN12624000006549)

P1/2, N=60, Recruiting, Australasian Leukaemia & Lymphoma Group | Not yet recruiting --> Recruiting

2 months ago

Enrollment open

NPM1 (Nucleophosmin 1)

NPM1 mutation

Venclexta (venetoclax) • cytarabine

2ms

Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. (PubMed, Lancet Oncol)

Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia. Phase 2 assessment of ziftomenib combination therapy in the upfront and relapsed or refractory setting is ongoing.

2 months ago

P1 data • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement • MLL mutation

ziftomenib (KO-539)

2ms

Recent progress in AML with recurrent genetic abnormalities. (PubMed, Int J Hematol)

However, resistance to targeted therapies is also a challenge. This Progress in Hematology features current trends and challenges in favorable-risk AML and FLT3 mutations that are frequently identified in these patients.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

FLT3 mutation • NPM1 mutation • CEBPA mutation

2ms

Chronic myelomonocytic leukemia with NPM1 mutation or acute myeloid leukemia? (PubMed, Oncologist)

Therefore, we describe a case of a patient diagnosed with CMML NPM1mut and briefly review the literature to highlight the uncertainty about how to classify a CMML with NPM1 mutation. We emphasize the importance of a comprehensive molecular study, which is crucial to optimize the individualized treatment of patients, enabling them to access targeted therapies.

2 months ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

2ms

Measurable Residual Disease Monitoring in AML With FLT3-ITD Treated With Intensive Chemotherapy Plus Midostaurin. (PubMed, Blood Adv)

NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk of relapse and death following intensive chemotherapy plus midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, clinically highly relevant target for MRD monitoring.

2 months ago

Journal

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

FLT3-ITD mutation • NPM1 mutation

Rydapt (midostaurin)