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    BIOMARKER:

    NUP214-ABL1 fusion

    i
    Other names: NUP214, Nucleoporin 214, Nuclear Pore Complex Protein Nup214, CAN Protein, Putative Oncogene, Nucleoporin 214kDa, CAIN, Nucleoporin 214kD (CAIN), 214 KDa Nucleoporin, Nucleoporin Nup214, Protein CAN, IIAE9, ABL proto-oncogene 1, ABL, c-ABL, JTK7, p150, ABL1
    Entrez ID:
    25; 8021
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1year
    Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia (ASH 2023)
    Pts received hyper-CVAD alternating with high-dose methotrexate (MTX) and cytarabine (Ara-C) for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...One pt discontinued blinatumomab due to a related adverse event (grade 2 encephalopathy and dysphasia). No pts discontinued INO due to toxicity, and no cases of veno-occlusive disease have been observed.
    Clinical • P2 data
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • NUP214 (Nucleoporin 214)
    |
    TP53 mutation • KMT2A rearrangement • MLL rearrangement • TP53 expression • CRLF2 overexpression • NUP214-ABL1 fusion • ABL1 fusion
    |
    Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
    over1year
    HYPER-CVAD WITH BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN FOR PATIENTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE II STUDY (EHA 2023)
    Pts received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...In pts with newly diagnosed Ph-negative B-cell ALL receiving hyper-CVAD with sequential blinatumomab, the addition of INO is safe and may improve survival. Acute lymphoblastic leukemia, Clinical trial, Phase II
    Clinical • P2 data
    |
    ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • NUP214 (Nucleoporin 214)
    |
    KMT2A rearrangement • MLL rearrangement • NUP214-ABL1 fusion • ABL1 fusion
    |
    Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
    over1year
    HEM-iSMART B: HEM-iSMART-B: Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies (clinicaltrials.gov)
    P1/2, N=26, Not yet recruiting, Princess Maxima Center for Pediatric Oncology
    New P1/2 trial
    |
    ABL1 (ABL proto-oncogene 1) • ETV6 (ETS Variant Transcription Factor 6) • NUP214 (Nucleoporin 214) • SATB1 (SATB Homeobox 1)
    |
    NUP214-ABL1 fusion • ABL1 fusion
    |
    Venclexta (venetoclax) • dasatinib • cytarabine • cyclophosphamide • dexamethasone • dexamethasone injection
    2years
    The Addition of Inotuzumab Ozogamicin to Hyper-CVAD Plus Blinatumomab Further Improves Outcomes in Patients with Newly Diagnosed B-Cell Acute Lymphoblastic Leukemia: Updated Results from a Phase II Study (ASH 2022)
    Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m2)...Beginning with pt #39, INO at a dose of 0.3 mg/m2 on day 1 and 8 was added to the 2 cycles of MTX/Ara-C and to 2 cycles of blinatumomab consolidation (4 total cycles with INO)... The addition of INO to hyper-CVAD with sequential blinatumomab is safe and highly effective as frontline treatment of Ph-negative B-cell ALL. This study shows the feasibility of incorporating both INO and blinatumomab into the frontline treatment of pts with B-cell ALL. Outcomes of the pts treated in the INO cohort are particularly promising.
    Clinical • P2 data
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • NUP214 (Nucleoporin 214) • POMP (Proteasome Maturation Protein)
    |
    TP53 mutation • KMT2A rearrangement • MLL rearrangement • NUP214-ABL1 fusion • ABL1 fusion
    |
    Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
    over2years
    Chemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy. (PubMed, Oncologist)
    The addition of dasatinib targeting NUP214-ABL1 to inotuzumab resulted in complete molecular remission, but recurrence occurred rapidly with dasatinib alone. However, deep molecular remission was recaptured with a combination of blinatumomab and ponatinib, so he could proceed to allotransplantation. This case illustrates that next-generation sequencing approaches designed to discover cryptic gene fusions can benefit patients with Ph-like ALL.
    Journal • IO biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NUP214 (Nucleoporin 214)
    |
    NUP214-ABL1 fusion • ABL1 fusion • BCR expression
    |
    dasatinib • Iclusig (ponatinib) • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin)
    over2years
    HYPER-CVAD WITH SEQUENTIAL BLINATUMOMAB, WITH OR WITHOUT INOTUZUMAB OZOGAMICIN, IN ADULTS WITH NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2022)
    Pts received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to 4 cycles, followed by 4 cycles of blinatumomab at standard doses. Pts with CD20+ disease (≥1% cells) received 8 doses of ofatumumab (2000 mg) or rituximab (375 mg/m 2 )...Conclusion Hyper-CVAD with sequential blinatumomab, with or without INO, is highly effective as frontline treatment of Ph-negative B-cell ALL, with an overall MRD negativity rate of 95% and a 3-year OS rate of 85%. Early outcomes with the addition of INO to this regimen are encouraging, with no relapses or deaths observed to date.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • CD20 (Membrane Spanning 4-Domains A1) • NUP214 (Nucleoporin 214) • POMP (Proteasome Maturation Protein)
    |
    NUP214-ABL1 fusion • ABL1 fusion
    |
    Rituxan (rituximab) • cytarabine • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Arzerra (ofatumumab) • methotrexate IV
    over2years
    NUP214-ABL1 fusion in childhood T-ALL. (PubMed, Pediatr Blood Cancer)
    No abstract available
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • NUP214 (Nucleoporin 214)
    |
    NUP214-ABL1 fusion • ABL1 fusion
    3years
    Clinico-Hematological Profile and Copy Number Abnormalities in a Cohort of STIL-TAL1 and NUP214-ABL1 Positive Pediatric T-Cell Acute Lymphoblastic Leukemia. (PubMed, Indian J Hematol Blood Transfus)
    NUP214-ABL1 fusion gene did not reveal any association with either CNVs or with survival. Although limited with the small cohort size and follow up, our study supports the similar frequency of these fusions as compared to other Asian and Western studies and also highlights utility of MLPA technique as a good diagnostic modality to screen for both STIL-TAL1 and NUP214-ABL1 fusions in a single assay with additional data on secondary copy number changes.
    Clinical • Journal
    |
    ABL1 (ABL proto-oncogene 1) • PTEN (Phosphatase and tensin homolog) • NUP214 (Nucleoporin 214)
    |
    NUP214-ABL1 fusion • ABL1 fusion
    4years
    [VIRTUAL] Next Generation Genomic Analyses in T-ALL Patients Identify Recurrent and Novel Genomic Abnormalities (ASH 2020)
    The top 20 mutated genes in our patient cohort differ to those reported for a pediatric cohort (Roberts et al 2019 Blood 134:649), indicating an association between patient age and genomic alteration. Secondary PDX models investigating novel targeted treatment strategies are ongoing.
    Clinical • BRCA Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • 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) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • AFF1 (AF4/FMR2 Family Member 1) • IL7R (Interleukin 7 Receptor) • JAK3 (Janus Kinase 3) • NUP214 (Nucleoporin 214) • TYK2 (Tyrosine Kinase 2) • LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • SMARCD1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily D, Member 1)
    |
    KRAS mutation • PTEN deletion • CDKN2A deletion • JAK3 mutation • NUP214-ABL1 fusion • ABL1 deletion • MLL3 deletion