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GENE:

NPM1 (Nucleophosmin 1)

News alerts, weekly reports and conference planners

Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review. (PubMed, J Cutan Pathol)

In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK-fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion.

2 days ago

Clinical • Review • Journal

ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • TPM3 (Tropomyosin 3) • DCTN1 (Dynactin Subunit 1) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • CLIP1 (CAP-Gly Domain Containing Linker Protein 1) • EHBP1 (EH Domain Binding Protein 1) • MLPH (Melanophilin) • RAB27A (RAB27A, Member RAS Oncogene Family)

ALK fusion • NPM1-ALK fusion

SOHO State of the Art Updates and Next Questions: Pre-emptive Therapy at Molecular Measurable Residual Disease Failure in Acute Myeloid Leukemia. (PubMed, Clin Lymphoma Myeloma Leuk)

In acute promyelocytic leukemia, arsenic trioxide-based regimen for MRD failure following frontline treatment with all-trans-retinoic acid plus chemotherapy represents standard of care, while hypomethylating agents (eg, azacitidine), salvage chemotherapy (eg, FLAG-IDA) and venetoclax-based regimens are effective in NPM1-mutated AML. Enrollment into clinical trials with genomic-guided assignment of pre-emptive therapy at MRD failure should be prioritized. Finally, with the emergence of novel agents (eg, menin inhibitors) and approaches (eg, adoptive cellular and immunological therapy), an exciting future lies ahead where a broad array of highly active pre-emptive therapeutic options will likely be clinically applicable to a wide range of AML subsets.

3 days ago

Review • Journal • IO biomarker

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

FLT3 mutation • NPM1 mutation

Venclexta (venetoclax) • azacitidine • arsenic trioxide

Transplant in AML: just follow the NPM1 guide! (PubMed, Blood)

No abstract available

6 days ago

Journal

NPM1 (Nucleophosmin 1)

Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients. (PubMed, Ann Hematol)

No significant difference was observed in OS and EFS between patients with NPM1A - type mut and NPM1non - A-type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.

6 days ago

Journal

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

FLT3-ITD mutation • NPM1 mutation

The Menin story in acute myeloid leukaemia-The road to success. (PubMed, Br J Haematol)

Other HOX and MEIS1 expressing leukaemias may also be sensitive to Menin inhibition. Following the encouraging results as monotherapy in refractory and relapsed AML, the combination of Menin inhibitors with chemotherapeutic agents and other targeted drugs is being investigated clinically.

8 days ago

Review • Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1) • PBX3 (PBX Homeobox 3)

NPM1 mutation • MLL rearrangement • MLL mutation • MLL fusion

Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study. (PubMed, Br J Haematol)

Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

9 days ago

Retrospective data • Journal

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

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

11d

Phosphorylation code of human nucleophosmin includes four cryptic sites for hierarchical binding of 14-3-3 proteins. (PubMed, J Mol Biol)

As three of these 14-3-3 binding phospho-sites in NPM1 reside within signal sequences, this work suggests a mechanism of NPM1 regulation by which NPM1 phosphorylation can promote 14-3-3 binding to affect NPM1 shuttling between cell compartments. It also provides further evidence that phosphorylation-induced structural rearrangements of globular proteins serve to expose otherwise cryptic 14-3-3-binding sites that are important for cellular function.

11 days ago

Journal

NPM1 (Nucleophosmin 1)

12d

Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies. (PubMed, Cell Death Discov)

A completely new activity of FOXM1, mediated through steroid/cholesterol biosynthetic process and protein secretion in cancer cells was also detected. Collectively, STL001 offers intriguing translational opportunities as combination therapies targeting FOXM1 activity in a variety of human cancers driven by FOXM1.

12 days ago

Journal

NPM1 (Nucleophosmin 1) • FOXM1 (Forkhead Box M1)

NPM1 mutation • FOXM1 overexpression

fenretinide nanoparticle (ST-001 nanoFenretinide)

14d

Molecular, clinical and therapeutic determinants of outcome in NPM1 mutated AML. (PubMed, Blood)

However, apart from the few patients with adverse cytogenetics, we could not identify any group of MRD negative patients with a CIR >40% or with benefit from allograft in first remission. Intensified chemotherapy with the FLAG-Ida regimen was associated with improved outcomes in all subgroups, with greater benefits observed in the highest risk molecular subgroups.

14 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • WT1 (WT1 Transcription Factor)

FLT3-ITD mutation • NPM1 mutation

14d

Genetic mutations and immune microenvironment: unveiling the connection to AML prognosis. (PubMed, Hematology)

The distribution of NK cells show significant differences among AML patients in different survival periods. This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.

14 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

16d

The effects of histidine substitution of aromatic residues on the amyloidogenic properties of the fragment 264-277 of nucleophosmin 1. (PubMed, Bioorg Chem)

The results clearly indicate that both the type of aromatic mutated residue and its position can have different effect on amyloid-like behaviors. They corroborate the crucial role exerted by Tyr271 in the self-assembling process of CTD of NPM1 in AML mutated form and add novel insights in the accurate investigation of how side chain orientations can determine successful design of innovative bioinspired materials.

16 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

19d

FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia. (PubMed, Curr Issues Mol Biol)

The FLT3 and IRAK4 inhibitor emavusertib (CA4948), the MCL1 inhibitor S63845, the BCL2 inhibitor venetoclax, and the HSP90 inhibitor PU-H71 were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells in vitro. The combination of CA4948 and BH3-mimetics may be effective in the treatment in FLT3-mutated AML with differential target specificity for MCL1 and BCL2 inhibitors. Moreover, the combination of CA4948 and PU-H71 may be a candidate combination treatment in FLT3-mutated AML.

19 days ago

Journal • Combination therapy • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • CD34 (CD34 molecule) • ITGAM (Integrin, alpha M) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation

Venclexta (venetoclax) • S63845 • emavusertib (CA-4948) • zelavespib intravenous (PU-H71 IV)

20d

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

20 days ago

Retrospective data • Journal

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor) • GATA2 (GATA Binding Protein 2)

NRAS mutation • GATA2 mutation

21d

A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia. (PubMed, Hematol Rep)

To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.

21 days ago

Review • Journal

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

NPM1 mutation • MLL rearrangement • KMT2A expression

revumenib (SNDX-5613) • ziftomenib (KO-539)

23d

Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. (PubMed, Pediatr Blood Cancer)

EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.

23 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

KMT2A rearrangement • MLL rearrangement

Mylotarg (gemtuzumab ozogamicin)

26d

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin. (PubMed, Int J Biol Sci)

Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

26 days ago

Journal

NPM1 (Nucleophosmin 1)

lovastatin

27d

Diagnostic utility of immunohistochemistry in detection of NPM1 mutations in acute myeloid leukemia with a patchy distribution. (PubMed, EJHaem)

We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

27 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

28d

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach. (PubMed, Int J Mol Sci)

Our findings underscore the complexity of NPM1-mutated AML, supporting the incorporation of advanced technologies for precise risk stratification and personalized therapeutic strategies. The study provides a foundation for future investigations into the clinical implications of identified genetic variations and highlights the importance of evolving diagnostic approaches in leukemia management.

28 days ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. (PubMed, Cancers (Basel))

The impact of revumenib on KMT2Ar or NPM1c AML cells was significantly enhanced when combined with tamibarotene, demonstrating synergistic differentiation or apoptosis initiation. These findings propose promising strategies for relapsed/refractory AML patients with defined molecular characteristics.

1 month ago

Journal

NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • RARA (Retinoic Acid Receptor Alpha) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NPM1 mutation • KMT2A rearrangement • MLL rearrangement

revumenib (SNDX-5613) • Amnolake (tamibarotene)

Mitoxantrone Versus Liposomal Daunorubicin in Induction of Pediatric AML With Risk Stratification Based on Flow Cytometry Measurement of Residual Disease. (PubMed, J Clin Oncol)

The intensification of induction therapy with risk stratification on the basis of response to induction and hSCT for high-risk patients led to improved outcomes. Mitoxantrone had a superior anti-leukemic effect than liposomal daunorubicin.

1 month ago

Journal

NPM1 (Nucleophosmin 1)

FLT3 wild-type

etoposide IV • mitoxantrone

Myeloid neoplasms in inflammatory bowel disease: A case series and review of the literature. (PubMed, Leuk Res Rep)

No IBD characteristic was found to associate with MN disease severity, including the previously-identified association between MNs and thiopurine exposure. Of the somatic mutations identified in out cohort's MN, mutations in TET2 were most prevalent, followed by FLT3-ITD, BCR-ABL, and NPM1 mutations.

1 month ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

FLT3-ITD mutation • NPM1 mutation • TET2 mutation

Unlocking the potential: A novel prognostic index signature for acute myeloid leukemia. (PubMed, Comput Biol Med)

Finally, to facilitate broader access to our findings, a user-friendly and publicly accessible webserver was established and available at http://bioinfor.imu.edu.cn/amlpi. This server provides tools including TME-related AML driver genes mining, AMLPI construction, multi-dimensional validations, AML patients risk assessment, and figures drawing.

1 month ago

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

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • PD-1 (Programmed cell death 1) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • SPATS2L (Spermatogenesis Associated Serine Rich 2 Like)

TP53 mutation • NPM1 mutation • PD-1 expression

Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance (clinicaltrials.gov)

P2, N=107, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting

1 month ago

Enrollment closed

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

FLT3-ITD mutation • NPM1 mutation • CEBPA mutation

cytarabine • Rydapt (midostaurin)

2ms

Differential prognostic values of the three AKT isoforms in acute myeloid leukemia. (PubMed, Sci Rep)

Curiously, although modestly varying among AML samples, a high AKT1 expression shows in contrast as a strong predictor of a better patient outcome. These data suggest that AKT3 and AKT1 expressions have strong, yet opposite, prognostic values.

2 months ago

Journal

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) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • AKT3 (V-akt murine thymoma viral oncogene homolog 3)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • BCOR mutation • AKT2 expression • AKT3 expression

2ms

CR108998: A Study of JNJ-75276617 in Participants With Acute Leukemia (clinicaltrials.gov)

P1/2, N=150, Recruiting, Janssen Research & Development, LLC | Phase classification: P1 --> P1/2

2 months ago

Phase classification

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

JNJ-6617

2ms

Kinome expression profiling improves risk stratification and therapeutic targeting in myelodysplastic syndromes. (PubMed, Blood Adv)

By investigating the Genomics of Drug Sensitivity in Cancer (GDSC) database, we identified axitinib and taselisib as candidate compounds that could potentially target the KISS-high myeloblasts. Altogether, our findings suggest that KISS holds the potential to improve the current prognostic scheme of MDS and inform novel therapeutic opportunities.

2 months ago

Journal

TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • STAG2 (Stromal Antigen 2) • PTK7 (Protein Tyrosine Kinase 7) • MAST4 (Microtubule Associated Serine/Threonine Kinase Family Member 4) • PAK6 (P21 (RAC1) Activated Kinase 6)

TP53 mutation • STAG2 mutation

Inlyta (axitinib) • taselisib (GDC-0032)

2ms

Comparison of clinical outcomes of several risk stratification tools in newly diagnosed AML patients: A real-world evidence in our current therapeutic era. (PubMed, Cancer Med)

Using Akaike's information criteria (AIC) to compare all five classifiers, ELN 2022 is the best classifier into younger and older patients and for prognosis.

2 months ago

Clinical data • Journal • HEOR • Real-world evidence • Real-world

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

TP53 mutation • NPM1 mutation • DNMT3A mutation

2ms

Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion (PubMed, Zhonghua Xue Ye Xue Za Zhi)

In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

2 months ago

Journal

ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PHF6 (PHD Finger Protein 6)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • PHF6 mutation • ABL1 fusion

2ms

Diverse functions of cytochrome c in cell death and disease. (PubMed, Cell Death Differ)

Furthermore, we provide an overview of the latest advanced technologies utilized for detecting cytochrome c, along with potential therapeutic approaches related to this protein. These strategies hold tremendous promise in personalized health care, presenting opportunities for targeted interventions in a wide range of conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer.

2 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • APAF1 (Apoptotic peptidase activating factor 1)

NPM1 mutation

2ms

Automated manufacture of ΔNPM1 TCR-engineered T cells for AML therapy. (PubMed, Mol Ther Methods Clin Dev)

ΔNPM1 TCR CD8 T cells manufactured with the optimized process showed specific killing of AML in vitro and in vivo. The process has been implemented in an upcoming phase 1/2 clinical trial for the treatment of NPM1-mutated AML.

2 months ago

Journal

NPM1 (Nucleophosmin 1) • CD8 (cluster of differentiation 8)

NPM1 mutation • CD8 positive

2ms

Dosing of 7 + 3 induction chemotherapy in a patient with acute myeloid leukemia (AML) and morbid obesity. (PubMed, J Oncol Pharm Pract)

This case suggests that dose capping of anthracyclines in the treatment of newly diagnosed AML may be an effective and safe treatment alternative in those with extreme BMI elevations beyond what has been studied in the literature. Given the increasing incidence of morbid obesity, further studies are needed to confirm appropriate dosing of anthracycline-based regimens at upper BMI extremes (>60 kg/m2).

2 months ago

Journal

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

IDH2 mutation • NPM1 mutation

cytarabine • daunorubicin

2ms

Quantifying NPM1 MRD in AML patients prior to allogeneic stem cell transplantation: Where to draw the line? (PubMed, Hemasphere)

No abstract available

2 months ago

Journal

NPM1 (Nucleophosmin 1)

2ms

Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis. (PubMed, Front Oncol)

This meta-analysis sheds light on the prevalence of genetic mutations in AML patients with MS, providing insights into the unique characteristics of the mutations and their frequencies. These discoveries are crucial in informing therapeutic and prognostic decisions for individuals with myeloid sarcoma.

2 months ago

Retrospective data • Review

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NRAS mutation • FLT3-ITD mutation • IDH2 mutation • CEBPA mutation

2ms

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)

P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

2 months ago

Trial completion date • Trial primary completion date

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)

HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation

2ms

Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)

P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027

2 months ago

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation

daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)

2ms

RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation. (PubMed, Br J Cancer)

The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.

2 months ago

Journal • Metastases

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • HDAC5 (Histone Deacetylase 5)

5-fluorouracil • oxaliplatin

2ms

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.

2 months ago

Journal

NPM1 (Nucleophosmin 1) • WT1 (WT1 Transcription Factor)

WT1 mutation

2ms

Regulation of HOX gene expression in AML. (PubMed, Blood Cancer J)

Recent identification of the menin-MLL interaction as a critical vulnerability of HOX-dependent AML has fueled the development of menin inhibitors that are clinically active in NPM1 and MLL rearranged AML despite inconsistent suppression of the HOX locus. Insights into context-specific regulation of HOX in AML may provide a solid foundation for targeting this common vulnerability across several major AML subtypes.

2 months ago

Review • Journal

NPM1 (Nucleophosmin 1) • FOXM1 (Forkhead Box M1)

NPM1 mutation • MLL rearrangement

2ms

BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor. (PubMed, Blood)

Compared to each drug, co-treatment with FHD-286 and BETi, MI, decitabine or venetoclax significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with MLL1r or mtNPM1.

2 months ago

Preclinical • Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)

NPM1 mutation • MLL rearrangement • MLL rearrangement

Venclexta (venetoclax) • decitabine • FHD-286

2ms

Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial) (clinicaltrials.gov)

P2, N=153, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

2 months ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • FLT3-TKD mutation • CEBPA mutation

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Starasid (cytarabine ocfosfate)

2ms

Hypomethylating Agents and Venetoclax for Acute Myeloid Leukemia Relapsed After Hematopoietic Stem Cell Transplant. (PubMed, Clin Lymphoma Myeloma Leuk)

These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.

2 months ago

Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation

Venclexta (venetoclax) • azacitidine • decitabine

2ms

Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC). (PubMed, J Clin Oncol)

For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.

2 months ago

P2 data • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

NPM1 mutation

Venclexta (venetoclax) • cytarabine