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    BIOMARKER:

    NPM1-ALK fusion

    i
    Other names: Nucleophosmin (Nucleolar Phosphoprotein B23, Numatrin), Testicular Tissue Protein Li 128, Nucleolar Protein NO38, Numatrin, NPM1, Nucleophosmin 1, Nucleophosmin/Nucleoplasmin Family, Member 1, Nucleolar Phosphoprotein B23, NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor
    Entrez ID:
    238; 4869
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    11ms
    Endogenous CD4 T cells that recognize ALK and the NPM1::ALK fusion protein can be expanded from human peripheral blood. (PubMed, Cancer Immunol Res)
    The NPM1::ALK fusion-specific TCR was HLA-DR13 restricted and conferred antigen specificity when expressed in a TCR- reporter cell line (58--). Together, our data provide evidence of ALK-specific CD4+ T cells in human peripheral blood, describe target epitopes in patients and support the consideration of CD4+ T cells in the development of ALK-specific immunotherapies.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    ALK positive • ALK fusion • NPM1-ALK fusion
    1year
    ALK-positive large B-cell lymphoma: a clinicopathological and molecular characteristics analysis of seven cases. (PubMed, Pathology)
    We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.
    Journal • IO biomarker
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • CLTC (Clathrin Heavy Chain) • CHD2 (Chromodomain Helicase DNA Binding Protein 2) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1) • SEC31A (SEC31 Homolog A COPII Coat Complex Component)
    |
    ALK positive • ALK rearrangement • ALK fusion • TET2 mutation • NPM1-ALK fusion
    over1year
    Racial Differences in ALK Gene Alterations Detected by Tissue and Liquid Biopsy Across Patients with Lung Cancer. (IASLC-WCLC 2024)
    Some atypical fusion partners were observed in white and BAA that were not observed in other races. These data emphasize the importance of testing lung cancer patients with assays that allow for unbiased fusion detection and identification of novel fusion partners across racially diverse populations to better understand racial and ethnic differences in ALK-rearranged lung cancers.
    Clinical • Liquid biopsy • Biopsy
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha)
    |
    TP53 mutation • ALK rearrangement • EML4-ALK fusion • ALK fusion • NPM1-ALK fusion • ALK amplification
    |
    Tempus xT Assay
    over1year
    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.
    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
    almost2years
    Variant ALK-fusion positive anaplastic large cell lymphoma (ALCL): A population-based paediatric study of the NHL-BFM study group. (PubMed, Br J Haematol)
    Five of eight patients with ATIC::ALK-positive ALCL relapsed, none of nine with TPM3::ALK. Variant ALK-partners are rare and potentially associated with different prognoses.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • TPM3 (Tropomyosin 3)
    |
    ALK positive • ALK fusion • NPM1-ALK fusion
    almost2years
    Molecular Screening in ALK-Positive Anaplastic Large Cell Lymphoma: ALK Analysis, NGS Fusion Gene Detection, and T-cell Receptor Immunoprofiling. (PubMed, Mod Pathol)
    NGS reveals new ALK translocation partners. Both the malignant and reactive TCR repertoires in ALK+ ALCL patients are unique and do not consistently occur among different patients.
    Journal • Next-generation sequencing • IO biomarker
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • TPM3 (Tropomyosin 3) • SQSTM1 (Sequestosome 1) • CLTC (Clathrin Heavy Chain) • CAPRIN1 (Cell Cycle Associated Protein 1) • SATB1 (SATB Homeobox 1) • TPM4 (Tropomyosin 4) • TRB (T Cell Receptor Beta Locus)
    |
    ALK positive • ALK rearrangement • ALK fusion • ALK translocation • NPM1-ALK fusion
    2years
    Circulating Tumor DNA (ctDNA) for Plasma Genotyping and Disease Monitoring in ALK-Positive Anaplastic Lymphoma (ALK+ALCL): A Proof of Concept Study (ASH 2023)
    Interestingly, CGP allowed the identification of the ALK:c.3520T>C; p.(Phe1174Leu) mutation in a plasma sample collected during disease progression while the patient was on long lasting crizotinib therapy...Additionally, our unique patient-specific ddPCR approach was proven to be a cost-effective method for MRD monitoring. Altogether, these findings serve as a proof-of-concept for the development of ctDNA techniques in the clinical management of ALK+ALCL.
    Tumor mutational burden • Circulating tumor DNA
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • LRP1B (LDL Receptor Related Protein 1B) • MDM4 (The mouse double minute 4) • EP300 (E1A binding protein p300) • TRAF1 (TNF Receptor Associated Factor 1) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • EEF1G (Eukaryotic Translation Elongation Factor 1 Gamma)
    |
    TP53 mutation • ALK positive • ALK rearrangement • ALK fusion • NPM1-ALK fusion
    |
    Xalkori (crizotinib)
    2years
    Comprehensive Mutational Profiling of Pediatric Acute Myeloid Leukemias Diagnosed at a Single Center (2022 WHO-HAEM5 Classification) (AMP 2023)
    Though <40% are cured after relapse in pAML, chemotherapy intensification is often not feasible, as toxicity causes ~10% mortality rate. Besides evaluating measurable residual disease, detecting unique driving events and concurrent molecular alterations impacts pAML management. Integration of genomic findings into clinical care for highrisk/refractory pAML patients, shows that ~14% can get targeted therapies.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • 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) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • WT1 (WT1 Transcription Factor) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • GATA1 (GATA Binding Protein 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MSI2 (Musashi RNA Binding Protein 2) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • PRDM16 (PR/SET Domain 16) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)
    |
    NPM1 mutation • ALK fusion • ALK mutation • KMT2A rearrangement • MLL rearrangement • CEBPA mutation • NPM1-ALK fusion
    over2years
    ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA WITH VARIANT ALK-FUSION PARTNER: A POPULATION-BASED ANALYSES OF THE NHL-BFM STUDY GROUP (ICML 2023)
    In our population-based cohort of ALK-positive ALCL-patients, less than 10% carried variant ALK-fusion partners, 60% of which were TPM3 or ATIC. In patients with exclusive cytoplasmic ALK staining patterns, NPM1::ALK positivity should be excluded by molecular analysis. The tendency of a different relapse risk between ATIC::ALK and TPM3::ALK -positive ALCL-patients suggests that the fusion partner might confer tumor aggressiveness or drug resistance.
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • TPM3 (Tropomyosin 3)
    |
    ALK positive • ALK rearrangement • ALK fusion • ALK translocation • NPM1-ALK fusion
    over2years
    IMPORTANCE OF ALK GENE SEQUENCING IN PEDIATRIC ANAPLASTIC LARGE CELL LYMPHOMA (ASPHO 2023)
    He achieved complete remission after 2 cycles with multi-agent chemotherapy (dexamethasone, ifosfamide, methotrexate, cytarabine, etoposide, cyclophosphamide, doxorubicin and brentuximab)...He had progressive disease after 3 weeks and was changed to combination chemotherapy with brentuximab and nivolumab with the addition of alectinib, a second generation ALK inhibitor. He again had progressive disease within 3 weeks and received therapy with ifosfamide, carboplatin and etoposide with a mixed response...Based on preclinical studies and limited clinical studies demonstrating that ALKI1171T mutations are resistant to crizotinib and alectinib but may maintain sensitivity to ceritinib, the patient started ceritinib in combination with brentuximab... Testing for the presence of ALK rearrangements via IHC is standard in pediatric ALCL but cannot solely predict sensitivity to specific inhibitors. Consideration should be made for upfront ALK gene sequencing as this may drive therapeutic decisions regarding which inhibitor is most likely to result in a clinical response.
    Clinical • PD(L)-1 Biomarker
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1)
    |
    ALK positive • ALK rearrangement • ALK fusion • ALK I1171T • ALK negative • NPM1-ALK fusion • ALK I1171 • NPM1-ALK I1171T
    |
    Opdivo (nivolumab) • Xalkori (crizotinib) • carboplatin • Alecensa (alectinib) • cytarabine • doxorubicin hydrochloride • Zykadia (ceritinib) • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • Adcetris (brentuximab vedotin)
    over2years
    Treatment-free remission after discontinuation of ALK tyrosine kinase inhibitors (TKIs) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) (AACR 2023)
    Out data demonstrated that treatment-free remission was durable for more than two years in ALK-positive ALCL patients following the cessation of ALK TKIs. MRD-guideddiscontinuation decision may be considered for ALK-positive ALCL patients treated with ALK inhibitors who had undetectable MRD.Table 1. Summary of patient characteristics and outcomes of ALK TKI discontinuationNo.SexAge at diagnosisAnn Arbor stageALK TKILines of prior therapyTreatment duration of ALK TKI (months)Reason for cessationDuration of ALK TKI cessation (months)Best response to ALK TKITime of MRD assessment after TKI cessationMRD after TKI cessation1M22IIBCrizotinib393.9Fertility27.8CR5.6Negative2F20IVBCrizotinib190.9Fertility25.9CR0.0Negative3M23IVCeritinib142.7Adverse event61.9CR61.9Negative4F58IVCrizotinib31.7Cost86.6CR72.1Negative5F64IVBCrizotinib113.6Cost31.0CR14.4Negative6M75IVCrizotinib211.7Cost80.2CR62.0Negative
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • NPM1 (Nucleophosmin 1) • E2F2 (E2F Transcription Factor 2)
    |
    ALK positive • ALK fusion • NPM1-ALK fusion • NPM-ALK fusion
    |
    Xalkori (crizotinib) • Zykadia (ceritinib)
    over2years
    Long-read sequencing of pediatric cancer genomes identifies multiple clinically relevant variants (AACR 2023)
    The difference in 5mC modification probability between the two alleles of the known imprinted genes was 81.5. Our results demonstrate that lrSeq can detect multiple CRGAs across several different types of genetic variants and pediatric cancers, bringing us closer to the promise of an all-in-one genetic test for cancer characterization.
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2A (Lysine Methyltransferase 2A) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    TP53 mutation • NTRK2 fusion • ALK fusion • CDKN2A deletion • KMT2A rearrangement • MLL rearrangement • NPM1-ALK fusion