News - NPM1 W288 - LARVOL VERI

10ms

Could Targeting NPM1c+ Misfolding Be a Promising Strategy for Combating Acute Myeloid Leukemia? (PubMed, Int J Mol Sci)

Our studies unveiled a direct link between AML mutations and the neat amyloidogenic character of the CTDs of NPM1c+. Herein, with the aim of exploiting these conformational features, novel therapeutic strategies are proposed that rely on the induction of the selective self-cytotoxicity of leukemic blasts by focusing on agents such as peptides, peptoids or small molecules able to enhance amyloid aggregation and targeting selectively AML-NPM1c+ mutations.

10 months ago

Review • Journal

NPM1 (Nucleophosmin 1)

NPM1 mutation • NPM1 W288

1year

NPM1 p.W288fs Variant Missed on Next-Generation Sequencing Analysis Because of “Strand Bias” (CAP 2023)

It is clinically critical to detect NPM1 variants in AML patients as it is associated with an overall favorable prognosis. We present a review of cases in which the NPM1 variant was missed and our strategy to deal with this. Myeloid NGS Cases in Which an NPM1 Variant Was Missed Because of Strand Bias

1 year ago

Next-generation sequencing

NPM1 (Nucleophosmin 1)

NPM1 mutation • NPM1 W288

almost2years

Acute Myeloid Leukemia with CEBPA Mutation: Next-Generation Sequencing-Based Computational Approach For Enhancing the Diagnosis of Patients with Potential Germline CEBPA Mutated Predisposition (USCAP 2023)

Recognizing and referring patients with possible germline mutations for appropriate genetic evaluation and testing provides insight into best patient care strategies along with education and testing opportunities for family members. Leukemia based NGS panels may aid as screening tools for detecting potential pathogenic germline variants.

almost 2 years ago

Clinical • Next-generation sequencing

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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KMT2C (Lysine Methyltransferase 2C) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CD36 (thrombospondin receptor) • MSH3 (MutS Homolog 3) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6) • BCORL1 (BCL6 Corepressor Like 1)

NRAS Q61 • CEBPA mutation • NRAS G13 • NRAS Q61L • DNMT3A R882H • IDH1 R132 • NRAS G13D • NRAS G13R • IDH2 R140Q • DNMT3A R882 • NPM1 W288

FoundationOne® Heme CDx

2years

Tracking Measurable Residual Disease in Acute Myeloid Leukemia with Error Corrected Sequencing (AMP 2022)

The MyMRD Myeloid Gene Panel Assay demonstrates excellent accuracy and high sensitivity in the detection of AML driver mutations at MRD levels. Its ability to reliably detect multiple mutations within one sample enables comprehensive myeloid studies.

2 years ago

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)

NPM1 W288

over2years

NGS VS PCR FOR THE DETECTION OF NPM1 GENE MUTATIONS IN ACUTE MYELOID LEUKEMIA. (EHA 2022)

AS-PCR could be effectively used for monitoring cases with standard inserts. However, NGS greatly facilitates non-standard inserts identification, appropriate allele-specific primers design for MRD analysis, and avoiding false-positive FA results for cases with intron localization of the insert.

over 2 years ago

Next-generation sequencing

NPM1 (Nucleophosmin 1)

NPM1 mutation • NPM1 W288

almost3years

Association of Next Generation Sequencing Based Genotypic Profiling with MICM Characteristics in NPM1 Mutated Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Co-existing FLT3-ITD in NPM1 AML independently predicts for CD34 and CD7, co-existing Ras-pathway mutation for HLA-DR and MPO, co-existing TET2/IDH1 mutation for CD34, CD7, and MPO, and co-existing DNMT3A mutation for HLA-DR, CD7, and MPO, thereby providing a new mechanism explanation for the immunophenotypic heterogeneity of these AML patients.

almost 3 years ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule) • CD7 (CD7 Molecule)

KRAS mutation • FLT3-ITD mutation • IDH1 mutation • NPM1 mutation • DNMT3A mutation • TET2 mutation • DNMT3A R882 • NPM1 W288

almost3years

Genomic Analysis of NPM1 Mutation and KMT2A (MLL )-Rearrangement/Amplification in Japanese Patients with Acute Myeloid Leukemia: Hematologic Malignancies (HM)-Screen-Japan 01 (ASH 2021)

Approximately three in ten patients with AML had NPM1 mutation and/or KMT2A (MLL )-rearrangement/amplification. No single patient had both the alterations. FLT3 and DNA methylation-associated genes (e.g., DNMT3A and TET2 ) were frequently seen in patients with NPM1 mt.

almost 3 years ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • 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) • NF1 (Neurofibromin 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

TP53 mutation • KRAS mutation • NPM1 mutation • DNMT3A mutation • KMT2A rearrangement • MLL rearrangement • MLL rearrangement • KMT2A mutation • MLL mutation • MLL fusion • MLL-MLLT3 fusion • NPM1 W288

FoundationOne® Heme CDx

3years

Single Cell Sequencing of Pediatric Acute Myeloid Leukemia Reveals Clonal Evolution to Relapse on Combination Chemotherapy with Sorafenib (ASH 2021)

SCS allows for direct measurement of clonal hierarchy and evolution, phylogeny, co-mutational status, and zygosity, which can only be inferred through traditional bulk NGS. The mutational mechanisms of resistance seen in adult leukemias treated with sorafenib monotherapy are not necessarily relevant to the pediatric population; rather than on-target FLT3 mutations, off target mutations including NRAS are found. This corroborates prior findings that off-target RAS pathway mutations may drive resistance to FLT3i.

3 years ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor) • SH2B3 (SH2B Adaptor Protein 3)

NRAS mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • TET2 mutation • WT1 mutation • NPM1 W288

sorafenib

3years

Comprehensive analysis of mutations and clonal evolution patterns in a cohort of patients with cytogenetically normal acute myeloid leukemia. (PubMed, Mol Cytogenet)

The findings of this study suggest that the relapse-initiating clones may pre-exist prior to therapy, which harbor or acquire mutations that confer selective advantage during chemotherapy, resulting in clonal expansion and eventually leading to relapse.

3 years ago

Clinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)

FLT3-ITD mutation • NPM1 mutation • NRAS G12D • NRAS G12 • IDH2 R140Q • NPM1 W288

over3years

[VIRTUAL] A CASE OF IDH1 MUTATED AML IN AN ADULT PATIENT AFFECTED BY OLLIER DISEASE, BIOLOGICAL SPECULATIONS AND CLINICAL IMPLICATIONS (EHA 2021)

Subsequently the patient underwent three consolidation cycles with HD Ara-C and midostaurin (days 8-21). It is important to note that the patient had remained free from leukaemia during three decades and a half, with AML developing only after acquisition of two other gene mutations (NPM1 and FLT3 TKD). These observations shed light on the paradigm of multiple genetic hits hypothesis of leukemogenesis and, after demonstration of the same IDH1 (R132H) mutation in chondroma tissue, prompt us to monitor the patient rather than candidate him to alloHCT in I CR.

over 3 years ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

IDH1 mutation • NPM1 mutation • FLT3-TKD mutation • FLT3 D835Y • IDH1 R132H • FLT3 D835 • FLT3 I836 • NPM1 W288

cytarabine • Rydapt (midostaurin)

4years

[VIRTUAL] Assessment of NTRK Alterations and TRK Inhibitor Therapy: A Single Center Experience (AMP 2020)

Our cohort displayed occurrence of NTRK fusions in a spectrum ranging from rare solid tumors (infantile fibrosarcoma >75% incidence) to AML (<5% incidence). Demonstration of the remarkable efficacy of larotrectinib and entrectinib in clinical trials led to their accelerated tissue-agnostic US Food and Drug Administration (FDA) approval for adult and pediatric patients with NTRK gene fusion solid tumors. Thus, it appears beneficial to screen all solid tumors without any known oncogenic driver for NTRK fusions.

4 years ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase)

TP53 mutation • NTRK1 fusion • NTRK3 fusion • NPM1 mutation • KRAS G13D • ETV6-NTRK3 fusion • KRAS G13 • TPM3-NTRK1 fusion • IDH2 R140Q • NPM1 W288 • NTRK positive • PIK3CA Q546R • miR-138 underexpression + miR-497 overexpression • NTRK fusion

Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)