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GENE:

NPM1 (Nucleophosmin 1)

News alerts, weekly reports and conference planners

Contribution of p53-dependent and -independent mechanisms to upregulation of p21 in Fanconi anemia. (PubMed, PLoS Genet)

In addition, we observed that reactive oxygen species (ROS) accumulation, another key feature of FA cells, is required to trigger an increase in PCNA/chromatin-associated p21 and to impact replication progression. Therefore, we propose a mechanism by which p21 and ROS cooperate to induce replication abnormalities that fuel genetic instability.

2 days ago

Journal

NPM1 (Nucleophosmin 1) • PCNA (Proliferating cell nuclear antigen) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MITF (Melanocyte Inducing Transcription Factor)

TP53 expression

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.

3 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

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.

3 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.

5 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.

6 days ago

Review • Journal

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

FLT3-ITD mutation • NPM1 mutation

Acute myeloid leukemia in the next-generation sequencing era : Real-world data from an Austrian tertiary cancer care center. (PubMed, Wien Klin Wochenschr)

Our study validates data from CCIT and supports their relevance for treatment decisions in a real-world setting. Moreover, they demonstrate the feasibility and benefits of NGS within a routine clinical setting.

7 days ago

Journal • Real-world evidence • Next-generation sequencing • Real-world

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

p14ARF forms meso-scale assemblies upon phase separation with NPM1. (PubMed, Nat Commun)

These hydrophobic interactions promote phase separation with NPM1, enhance p14ARF nucleolar partitioning, restrict NPM1 diffusion within condensates and nucleoli, and reduce cellular proliferation. Our structural analysis provides insights into the multifaceted chaperone function of NPM1 in nucleoli by mechanistically linking the nucleolar localization of p14ARF to its partial folding and meso-scale assembly upon phase separation with NPM1.

7 days ago

Journal

NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma. (PubMed, J Exp Clin Cancer Res)

Integrated studies define MYC inhibition by panobinostat as a novel treatment element to be introduced into the therapeutic strategy for patients with metastatic hepatoblastoma.

7 days ago

Journal • Metastases

NPM1 (Nucleophosmin 1)

cisplatin • doxorubicin hydrochloride • Farydak (panobinostat)

Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multi-center Cohort Study. (PubMed, Clin Cancer Res)

Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

7 days ago

Journal

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

KRAS mutation • FLT3-ITD mutation • FLT3 mutation • DNMT3A mutation • TET2 mutation

Venclexta (venetoclax) • azacitidine • Synribo (omacetaxine mepesuccinate)

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.

7 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.

7 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.

7 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Development and Performance of SNAQ-SEQ Spike-in Standards in AML NGS Diagnostic and MRD Testing (AMP 2024)

We have demonstrated that the addition of SNAQ-SEQ IS spike-in standards produced expected VAF in response to dilution, and for AML samples, provided a direct per sample 0.3% VAF sensitivity QC. The IS variants replace the need for an external positive reference run control sample, enabling an additional patient sample to be run to increase testing throughput, flow cell utilization, and reduced testing cost. Second, the ability to compare the known versus measured IS VAF conveys the reporting accuracy of the test on a per-sample basis.

9 days ago

Next-generation sequencing

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

Oncomine™ Myeloid MRD Assays

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.

9 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.

9 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

15d

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.

15 days ago

Retrospective data • Journal

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

FLT3-ITD mutation • NPM1 mutation

sorafenib

15d

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.

15 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

16d

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.

16 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

16d

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.

16 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

16d

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.

16 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

16d

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

16 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)

16d

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.

16 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

16d

Longitudinal Sequencing to Investigate Clonal Evolution in Myeloid Neoplasms (ASH 2024)

We analyzed 851 patients with MN at Karmanos Cancer Institute; 444 with serial samples. Among these patients, 174 (39%) had primary AML (pAML), 144 (32%) had secondary AML (sAML), 58 (13%) had MDS, 18 (4%) had MDS/MPN and 50 (11%) had MPN. Median age for primary AML was 56 ys (19-82), secondary AML was 64 ys (31-86) and MDS was 66 ys (23-90).

16 days ago

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2)

TP53 mutation • DNMT3A mutation • STAG2 mutation

TruSight Myeloid Sequencing Panel

16d

A multicentre clinical trial to assess the safety and tolerability of the combination of low-dose cytarabine or azacitidine, plus Venetoclax and Quizartinib in newly diagnosed acute myeloid leukemia patients aged equal or more than 60 years old ineligible for standard induction chemotherapy Ensayo clínico multicéntrico para evaluar la seguridad y la tolerabilidad de la combinación de azacitidina o citarabina en dosis bajas con Venetoclax y Quizartinib en pacientes de 60 años de edad o más con nuevo diagnóstico de leucemia mieloide aguda y no candidatos a inducción estándar con quimioterapia (clinicaltrialsregister.eu)

P1/2, N=84, Ongoing, Fundación Pethema

16 days ago

New P1/2 trial

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

Venclexta (venetoclax) • cytarabine • azacitidine • Vanflyta (quizartinib)

17d

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.

17 days ago

Review • Journal

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

NPM1 mutation

19d

Recurrent hepatocellular carcinoma is associated with the enrichment of MYC targets gene sets, elevated high confidence deleterious mutations and alternative splicing of DDB2 and BRCA1 transcripts. (PubMed, Adv Med Sci)

These results indicated that the enrichment of MYC targets gene sets is one of the most critical factors that leads to the development of recurrent HCC. In addition, elevated deleterious mutation numbers and alternative spliced DDB2 and BRCA1 isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC.

19 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • NPM1 (Nucleophosmin 1) • CD8 (cluster of differentiation 8) • CDK4 (Cyclin-dependent kinase 4) • DDB2 (Damage Specific DNA Binding Protein 2) • MCM4 (Minichromosome Maintenance Complex Component 4) • MCM5 (Minichromosome Maintenance Complex Component 5) • CBX3 (Chromobox 3)

BRCA1 mutation

23d

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.

23 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

23d

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.

23 days ago

P1 data • Journal • IO biomarker

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

IDH2 mutation • NPM1 mutation • IDH2 R140Q

24d

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.

24 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

25d

Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience. (PubMed, Medicine (Baltimore))

According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.

25 days ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6)

ASXL1 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • PHF6 mutation

26d

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.

26 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

26d

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.

26 days ago

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

NPM1 (Nucleophosmin 1)

NPM1 mutation

26d

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.

26 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)

26d

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.

26 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)

27d

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.

27 days ago

Review • Journal

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

NPM1 mutation • KMT2A mutation

29d

NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation. (PubMed, Leukemia)

The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions...Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.

29 days ago

Journal • IO biomarker

NPM1 (Nucleophosmin 1)

NPM1 expression

Xpovio (selinexor)

29d

CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov)

P1, N=200, Recruiting, Janssen Research & Development, LLC | N=150 --> 200

29 days ago

Enrollment change • Combination therapy

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

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • idarubicin hydrochloride • bleximenib (JNJ-6617)

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

1 month ago

New P3 trial • Combination therapy

NPM1 (Nucleophosmin 1)

NPM1 mutation

Venclexta (venetoclax) • azacitidine • Revuforj (revumenib)

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.

1 month 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

Correction for Garzon et al., Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. (PubMed, Proc Natl Acad Sci U S A)

No abstract available

1 month ago

Journal

NPM1 (Nucleophosmin 1)

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