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    BIOMARKER:

    MLL rearrangement

    i
    Other names: HTRX1, HTRX, MLL1A, Mixed Lineage Leukemia 1, Myeloid/Lymphoid Or Mixed-Lineage Leukemia Protein 1, CXXC7, MLL1, TRX1, Zinc Finger Protein HRX, Trithorax-Like Protein, ALL-1, Lysine (K)-Specific Methyltransferase 2A, CXXC-Type Zinc Finger Protein 7, Histone-Lysine N-Methyltransferase 2A, Myeloid/Lymphoid Or Mixed-Lineage Leukemia, Lysine Methyltransferase 2A, MLL, Myeloid/Lymphoid Or Mixed-Lineage Leukemia, KMT2A
    4d
    Integrated Cytogenetic and FISH Profiling Reveals inv(16) Dominance and Cryptic 11q23 Lesions in AML and ALL: Clinical Significance from a Referral Cohort. (PubMed, J Assoc Genet Technol)
    Conventional karyotyping and targeted FISH probes were employed to identify recurrent and rare chromosomal abnormalities, with a special emphasis on inv(16) (p13.1q22), MLL rearrangements, and complex karyotypes. Our findings highlight the indispensable role of integrating cytogenetics and FISH in routine diagnostic workflows, especially in cases with cryptic rearrangements or subclonal abnormalities, thereby underscoring their clinical and prognostic significance.
    Journal
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    KMT2A (Lysine Methyltransferase 2A)
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    MLL rearrangement
    6d
    Therapy-related myeloid neoplasms following treatment for high-risk gestational trophoblastic neoplasia: a case series and retrospective analysis. (PubMed, Int J Clin Oncol)
    Although combination chemotherapy remains essential for high-risk GTN, exposure to high cumulative doses of etoposide confers a risk of secondary t-MNs. Long-term hematologic surveillance and less leukemogenic strategies are warranted.
    Retrospective data • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • KMT2A (Lysine Methyltransferase 2A)
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    MLL rearrangement
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    etoposide IV
    13d
    AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov)
    P3, N=5949, Completed, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Mar 2026 | Active, not recruiting --> Completed
    Trial completion • Trial completion date
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
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    MLL rearrangement
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    dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    21d
    Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases (clinicaltrials.gov)
    P=N/A, N=200, Terminated, Masonic Cancer Center, University of Minnesota | Trial completion date: Feb 2028 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Feb 2027 --> May 2026; No longer a research question to answer.
    Trial completion date • Trial termination • Trial primary completion date
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    KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1)
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    MLL rearrangement
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    cyclophosphamide • fludarabine IV • cyclosporin A microemulsion
    1m
    The role of RAS mutations in leukemia progression, differentiation, and drug resistance. (PubMed, Leuk Res Rep)
    Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.
    Review • Journal • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1) • RAS (Rat Sarcoma Virus) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    KRAS mutation • NRAS mutation • FLT3-ITD mutation • KIT mutation • RUNX1 mutation • RAS mutation • MLL rearrangement • MLL mutation
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    Venclexta (venetoclax)
    2ms
    CD19-CAR_Lenti in pediatric patients affected by relapsed/refractory B-ALL or aggressive B-NHL (2024-519174-39-00)
    P1/2, N=32, Active, not recruiting, Ospedale Pediatrico Bambino Gesu | Recruiting --> Active, not recruiting
    Enrollment closed
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    TP53 (Tumor protein P53) • CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
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    MLL rearrangement
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    cyclophosphamide • fludarabine IV
    2ms
    Characterizing the impact of MLL fusion variants and fusion partners on leukemia plasticity using a human CRISPR-engineered MLL-rearranged leukemia model. (PubMed, Neoplasia)
    The cells still exhibited high lineage plasticity, switching from a myeloid to a B-lymphoid identity in vivo. In conclusion, this model enables the mechanistic dissection of MLL fusion variants in vitro and in vivo, providing a foundation for developing targeted therapies for MLL-rearranged leukemias.
    Journal
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    BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • CD34 (CD34 molecule) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
    |
    MLL rearrangement
    2ms
    Digital PCR of CHIP and MR for MRD Monitoring After Allo-HSCT in AML (clinicaltrials.gov)
    P=N/A, N=100, Recruiting, Peking University People's Hospital
    New trial • Tumor mutational burden • Minimal residual disease
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    ABL1 (ABL proto-oncogene 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • FUS (FUS RNA Binding Protein) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    NPM1 mutation • MLL rearrangement
    3ms
    Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
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    KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1)
    |
    MLL rearrangement
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    cyclophosphamide • fludarabine IV • cyclosporin A microemulsion
    3ms
    The oncogenic role of ecotropic viral integration site 1 in hematological malignancies: mechanisms of activation and leukemogenesis. (PubMed, Front Immunol)
    Clinically, EVI1 overexpression is one of the most robust independent indicators of poor prognosis, associated with therapy resistance and reduced overall survival. This review provides a detailed discussion of the mechanisms underlying EVI1's activation, its complex molecular functions in hematopoietic transformation, and its profound clinical implications in hematological malignancies.
    Review • Journal
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    PTEN (Phosphatase and tensin homolog) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    MLL rearrangement
    3ms
    Recent Advances and Perspectives of Small Molecule Modulators Targeting DOT1L. (PubMed, J Med Chem)
    Modulators targeting DOT1L have been developed for more than a decade, and compounds such as competitive inhibitors, protein-protein interaction (PPI) inhibitors, and degraders block DOT1L's pathogenic functions through various pharmacological mechanisms. Challenges and opportunities are discussed in this perspective, aiming to provide valuable insights for the future design of DOT1L modulators.
    Review • Journal
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    KMT2A (Lysine Methyltransferase 2A) • HOXA9 (Homeobox A9) • DOT1L (DOT1 Like Histone Lysine Methyltransferase)
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    MLL rearrangement
    4ms
    Overcoming Menin inhibitor resistance in AML cells with combinations including BET proteins and dual BRG1/BRM inhibitor. (PubMed, Blood)
    Compared to each drug alone, co-treatment with SNDX-5613 (revumenib) and FHD-286 or OTX015 and FHD-286 significantly reduced the in vivo AML burden and improved survival of the immune depleted mice, without inducing significant toxicity, in the xenograft models of MITR and MI-resistant PD MLL1-r AML cells. These findings highlight novel, targeted, drug combinations that overcome MI resistance in AML cells with MLL1-r or mtNPM1.
    Journal
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    NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1) • BRD4 (Bromodomain Containing 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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    NPM1 mutation • MLL rearrangement • MLL mutation
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    Revuforj (revumenib) • birabresib (OTX015) • camibirstat (FHD-286)