^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    AFF1 (AF4/FMR2 Family Member 1)

    i
    Other names: AFF1, AF4/FMR2 Family Member 1, ALL1-Fused Gene From Chromosome 4 Protein, Pre-B-Cell Monocytic Leukemia Partner 1, Proto-Oncogene AF4, MLLT2, PBM1, AF4, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax (Drosophila) Homolog); Translocated To 2, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog Drosophila); Translocated To 2, AF4/FMR2 Family Member 1, Protein AF-4, Protein FEL, FEL
    10d
    Analysis of ten cases of Acute lymphoblastic leukemia with non-KMT2A::AFF1 transcriptional variant 11q23 rearrangements (PubMed, Zhonghua Yi Xue Yi Chuan Xue Za Zhi)
    The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
    Retrospective data • Journal • IO biomarker
    |
    CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • KMT2A (Lysine Methyltransferase 2A) • CD38 (CD38 Molecule) • WT1 (WT1 Transcription Factor) • CD22 (CD22 Molecule) • AFF1 (AF4/FMR2 Family Member 1) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CD2 (CD2 Molecule) • AFDN (Afadin, Adherens Junction Formation Factor) • FUT4 (Fucosyltransferase 4) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    KMT2A rearrangement
    1m
    GREM1 promotes leukemic survival via PI3K/AKT signaling in infant MLL-AF4-positive B-ALL. (PubMed, Exp Hematol)
    Together, these findings identify GREM1 as a leukemia cell-associated regulator of survival in infant MLL-AF4-positive B-ALL and implicate PI3K/AKT signaling as a key downstream mediator, suggesting that GREM1-associated survival pathways may represent a potential vulnerability in this aggressive leukemia subtype. TEASER ABSTRACT: GREM1 is overexpressed in infant MLL-AF4-positive B-ALL and promotes leukemic cell survival by activating PI3K/AKT signaling, making it a potential therapeutic target.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • GREM1 (Gremlin 1)
    1m
    Intra-subtype heterogeneity shapes treatment response in KMT2A-rearranged ALL across all age groups. (PubMed, Hemasphere)
    Notably, good responders to ex vivo induction drugs were characterized by a higher maturity score (P = 1.8E-03), whereas for less mature KMT2Ar B-ALL cases, response profiles suggested higher Venetoclax sensitivity. Our study provides an integrative framework linking developmental phenotype, fusion partner, and MRD kinetics across the full age spectrum of KMT2Ar B-ALL. These insights may support future risk-adapted strategies and therapeutic targeting, particularly in immature KMT2Ar B-ALL.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1)
    |
    Venclexta (venetoclax)
    2ms
    Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia (clinicaltrials.gov)
    P1/2, N=20, Recruiting, University Hospital Tuebingen | Trial completion date: Mar 2027 --> Feb 2029 | Trial primary completion date: Mar 2027 --> Jul 2028
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
    |
    TP53 mutation • CD19 positive
    |
    Monjuvi (tafasitamab-cxix)
    2ms
    Research Progress on the KMT2A-AFF3 Fusion Gene in Childhood Acute Lymphoblastic Leukemia: Mechanisms, Clinical Implications, and Therapeutic Strategies. (PubMed, Curr Issues Mol Biol)
    This review highlights the evidence defining its poor prognosis, which is primarily driven by profound chemoresistance to conventional therapies, including glucocorticoids. Finally, we discuss the rapidly evolving therapeutic landscape, detailing the limitations of standard intensive chemotherapy and the immense promise of novel targeted strategies, such as Menin inhibitors (e.g., Revumenib), DOT1L inhibitors, and immunotherapies (e.g., CAR-T cells, Blinatumomab), which hold the potential to revolutionize outcomes for this high-risk leukemia subtype.
    Review • Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • MEIS1 (Meis Homeobox 1) • MME (Membrane Metalloendopeptidase) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • AFF3 (AF4/FMR2 Family Member 3)
    |
    Blincyto (blinatumomab) • Revuforj (revumenib)
    4ms
    Mixed-lineage leukaemia cells undergo unique adaptations in the CNS niche. (PubMed, Exp Hematol)
    These findings indicate that the CNS niche imposes selective pressures that cause lasting metabolic and functional reprogramming of leukemic cells, impairing their ability to reestablish systemic disease and potentially affecting immune cell interactions. Furthermore, these findings may be more generally relevant to primary mixed-lineage infant leukaemia and, increasingly important, lineage-switched infant leukaemia.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1)
    4ms
    Acute Myeloid Leukemia With KMT2A Rearrangement Presenting as Skin Hyperpigmentation. (PubMed, J Cutan Pathol)
    The patient was diagnosed with AML with an 11q23 KMT2A::AFF1 gene rearrangement-a mutation increasingly associated with a poor prognosis. This case underscores the importance of recognizing hyperpigmentation as a rare but potential manifestation of LC, especially in younger patients, and highlights the need for prompt diagnosis and intervention to improve patient outcomes.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • MPO (Myeloperoxidase)
    |
    KMT2A rearrangement
    4ms
    Blinatumomab-Related Lineage Switch of KMT2A/AFF1-Rearranged B-Lymphoblastic Leukemia to B/Myeloid Mixed-Phenotype Acute Leukemia and Myeloid Sarcoma Causing Spinal Cord Compression. (PubMed, Case Rep Hematol)
    It highlights an unusual and serious pattern of relapse in an extramedullary site following blinatumomab therapy. Clinicians should remain vigilant for signs of lineage switch and extramedullary disease during treatment, particularly in patients with KMT2A-rearranged B-ALL, and consider imaging or biopsy when new neurologic or systemic symptoms arise.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1)
    |
    KMT2A rearrangement
    |
    Blincyto (blinatumomab)
    5ms
    CRISPR/Cas9-mediated t(4;11) translocation in human hematopoietic stem/precursor cells demonstrates plasticity to differentiate into either the myeloid or lymphoid lineage. (PubMed, Leukemia)
    Thus, the CRISPR/Cas9 technique allowed us to create a bona fide model system to study the very early steps of leukemia onset at the molecular level. In conclusion, this approach is the fastest way to investigate and characterize KMT2A-r fusions in primary human cells.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • IL7 (Interleukin 7)
    6ms
    Flexible electrochemical biochip for multianalyte detection in childhood leukemia diagnosis. (PubMed, Bioelectrochemistry)
    The biochips achieved detection limits ranging from 9 to 29 copies of the oncogenes using label-free detection in 15 min. Therefore, the biochips developed in this study exhibit promising characteristics for the diagnosis of clinically relevant oncogenes.
    Journal
    |
    RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • AFF1 (AF4/FMR2 Family Member 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
    6ms
    Upfront Menin-inhibitor resistance in multiply pretreated leukemias. (PubMed, Exp Hematol)
    Future studies will need to clarify more broadly which genomic/epigenomic alterations drive upfront resistance. Regardless of mechanism, our data supports using Menin-inhibitors upfront or in early lines of therapy before substantial genomic or epigenomic evolution has occurred.
    Journal
    |
    TP53 (Tumor protein P53) • KMT2A (Lysine Methyltransferase 2A) • KMT2C (Lysine Methyltransferase 2C) • AFF1 (AF4/FMR2 Family Member 1) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    TP53 mutation