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    BIOMARKER:

    KMT2A rearrangement

    i
    Other names: KMT2A, Lysine Methyltransferase 2A, Histone-Lysine N-Methyltransferase 2A, CXXC7, TRX1, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila), Lysine (K)-Specific Methyltransferase 2A, CXXC-Type Zinc Finger Protein 7, Lysine N-Methyltransferase 2A, Zinc Finger Protein HRX, Trithorax-Like Protein, HTRX1, MLL1A, MLL1, MLL, Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax (Drosophila) Homolog), Myeloid/Lymphoid Or Mixed-Lineage Leukemia Protein 1, Myeloid/Lymphoid Or Mixed
    Entrez ID:
    4297
    Related biomarkers:
    Expression
    Mutation
    Fusion
    Others
    Related tests:
    1d
    Targeting menin for precision therapy in high-risk acute myeloid leukemia. (PubMed, Leuk Res Rep)
    The clinical promise of Revumenib in genetically defined AML highlights its potential role in shaping the future treatment landscape. This mini-review underscores the need for ongoing trials to define optimal dosing, safety protocols, and combination therapies, with the ultimate goal of establishing Revumenib as a standard of care for high-risk AML subsets.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Revuforj (revumenib)
    5d
    Menin Inhibitors: New Targeted Therapies for Specific Genetic Subtypes of Difficult-to-Treat Acute Leukemias. (PubMed, Cancers (Basel))
    MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEN1 (Menin 1)
    |
    KMT2A rearrangement • MLL rearrangement • MLL fusion
    |
    Revuforj (revumenib) • ziftomenib (KO-539)
    5d
    Lactylation modulation identifies key biomarkers and therapeutic targets in KMT2A-rearranged AML. (PubMed, Sci Rep)
    The study also suggested PI3K inhibitors and Pevonedistat as possible therapeutic options to modulate immune cell infiltration. Our findings confirm the critical role of lactylation in KMT2Ar-AML and identify six key genes that may serve as biomarkers for diagnosis and treatment. In addition to highlighting the need for further validation in clinical settings, these findings contribute to our understanding of KMT2Ar-AML's molecular mechanisms.
    Journal
    |
    LDHB (L-lactate dehydrogenase B chain) • KMT2A (Lysine Methyltransferase 2A) • PRDX1 (Peroxiredoxin 1) • LGALS1 (Galectin 1) • S100A6 (S100 calcium binding protein A6)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    pevonedistat (MLN4924)
    5d
    Prediction model establishment of prognosis factors for acute myeloid leukemia based on the SEER database. (PubMed, Sci Rep)
    Patients were classified into high-risk and low-risk groups based on nomogram scores, with significant differences in OS and CSS between these groups (P < 0.001). This study developed innovative nomograms that combine clinical and treatment factors to predict 1-, 3-, and 5-year survival rates for patients with t (9;11) (p22; q23) AML.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    16d
    The Factors Related to Treatment Failure in Children with Acute Lymphoblastic leukemia--Analysis of Multi-Center Data from Real World in Fujian Province (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    The treatment failure of children with ALL in our province is still relatively high, with relapse being the main cause of treatment failure, while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.
    Retrospective data • Journal • Real-world evidence
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    22d
    AALL15P1: Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and KMT2A Gene Rearrangement (clinicaltrials.gov)
    P2, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Nov 2025
    Trial completion date
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    cytarabine • azacitidine • cyclophosphamide • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
    24d
    Menin inhibitors in the treatment of acute myeloid leukemia. (PubMed, Blood)
    Menin inhibitors have emerged as a promising therapeutic approach, targeting key genetic drivers of AML such as KMT2A rearrangements and NPM1 mutations. Here, we review the clinical value of menin inhibitors, highlighting their mechanism of action, efficacy, safety, and potential to transform AML treatment.
    Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    29d
    Protocol for CRISPR-Cas9-mediated induction of KMT2A rearrangements in cell line and umbilical cord blood hematopoietic stem and progenitor cells. (PubMed, STAR Protoc)
    We describe steps for patient-specific single guide RNA (sgRNA) design, optimized sgRNA in vitro transcription, detailed purification of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB), and CRISPR-Cas9 editing of the test cell line K562 as well as UCB HSPCs. The provided methodology is donor independent.
    Preclinical • Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    1m
    Comprehensive Genomic Profiling (CGP) of Acute Myeloid Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)
    Current best practices for the diagnosis, classification, prognostication, and treatment of AML call for the assessment of the presence and absence of numerous genomic alterations. Therefore, in contrast to single-gene or small-panel molecular testing, the F1H platform can simplify such assessment via a CGP approach.
    IO biomarker
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)
    |
    TP53 mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • U2AF1 mutation • CEBPA mutation • MLL mutation • NPM1 W288
    |
    FoundationOne® Heme CDx
    2ms
    BRAF V600E-Mutant Acute Myeloid Leukemia: A Case Series and Literature Review of a Rare Entity. (PubMed, Genes (Basel))
    Although it is uncertain whether the complex karyotype and somatic mutations observed in case 1 and KMT2A rearrangement and variants identified in case 2 may have either independently or cooperatively conferred a poor prognosis, we contend that additional comprehensive studies are needed to further understand the pathophysiology and prognosis of BRAF mutations in AML. We further posit whether patients with BRAF V600E-mutant AML may benefit from the combined use of BRAF inhibitors and/or RAS-pathway-targeting regimens, which are currently FDA-approved for the treatment of BRAF V600-mutant solid tumors and BRAF-mutant histiocytic neoplasms.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    BRAF V600E • BRAF V600 • TET2 mutation • KMT2A rearrangement • KRAS G12A • KRAS G12 • MLL rearrangement • MLL rearrangement
    2ms
    Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead. (PubMed, J Hematol Oncol)
    More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.
    Review • Journal • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • cytarabine
    2ms
    A RUNX1: RUNX1T1 AML with a simultaneous false positive KMT2A rearrangement: FISH interpretation pitfalls. (PubMed, Hematology)
    Given that KMT2A FISH probes cover approximately 1 Mb around KMT2A, this subtle shift led to a split-apart signal pattern mimicking a genuine KMT2A rearrangement, resulting in a false positive FISH interpretation. This case highlights a false positive KMT2Ar in primary AML, indicating the need for additional molecular testing for confirmation.
    Journal
    |
    RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)
    |
    KMT2A rearrangement • MLL rearrangement • RUNX1-RUNX1T1 fusion • MLL fusion
    2ms
    Lineage Switch from Therapy-Related B Cell Acute Lymphoblastic Leukemia to Pure Erythroid Leukemia Following CD20-Directed Immunotherapy: A Mechanism for Immune Escape? (AMP 2024)
    Six weeks later, while receiving the CD20-directed immunotherapies glofitamab and obinutuzumab, another bone marrow biopsy revealed eradication of the B-ALL and new involvement by pure erythroid leukemia (PEL). This patient's B-ALL lacked an IGH::BCL2 fusion resulting from t(14; 18), suggesting it did not arise through transformation of his prior FL/DLBCL. Instead, the B-ALL was likely caused by his extensive exposure to genotoxic chemotherapy drugs – including alkylating agents – for his preceding lymphomas. The shared cytogenetic and molecular features between this patient's B-ALL and PEL imply they are clonally related.
    IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • KMT2A (Lysine Methyltransferase 2A)
    |
    TP53 mutation • KMT2A rearrangement • MLL rearrangement • BCL2 fusion
    |
    TruSight Myeloid Sequencing Panel
    |
    Gazyva (obinutuzumab) • Columvi (glofitamab-gxbm)
    2ms
    Evaluation of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 for Partner-Agnostic Fusion Gene Detection in Acute Leukemias (AMP 2024)
    We demonstrated the capability of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 to achieve 100% accurate detection for novel and canonical translocations. By allowing concurrent detection of multiple known and novel rearrangements, NGS assays offer an economical and efficient alternative to routine cytogenetic approaches.
    Next-generation sequencing
    |
    ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • HOXD8 (Homeobox D8)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    SureSeq™ Myeloid Fusion Panel
    2ms
    KMT2A (MLL1) Rearrangements in Hematolymphoid Malignancies: A Genomic Landscape Study (ASH 2024)
    Conclusions : Rearrangements in the KMT2A gene in AML are common and may emerge as a new target of therapy for AML patients. This genomic landscape study reveals significant differences in import GA associated with AML in KMT2Ara and KMT2Anra cases.
    Tumor mutational burden
    |
    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor)
    |
    KRAS G12C • KMT2A rearrangement • KRAS G12 • MLL rearrangement • MLL rearrangement • MLL mutation
    |
    FoundationOne® Heme CDx
    3ms
    CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy. (PubMed, J Immunother Cancer)
    To our knowledge, these are the first cases of LS to be reported in patients with CRLF2 rearranged acute lymphoblastic leukemia. In addition to raising awareness that this genetic mutation may associate with lineage plasticity, our cases illustrate the importance of multi-modal disease surveillance in the diagnosis of LS.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2)
    |
    KMT2A rearrangement • MLL rearrangement • CRLF2 rearrangement
    3ms
    Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia. (PubMed, Cancer Med)
    Studies indicate that KMT2A rearrangements are present in over 70% of infant leukemia cases, approximately 10% of adult AML cases, and numerous instances of secondary acute leukemias, making it a disease of critical concern to clinicians and researchers alike. The future of KMT2A-r acute leukemia research is characterized by an expanding knowledge of the disease's biology, with an emphasis on personalized therapies, immunotherapies, genomic advancements, and innovative therapeutic combinations. The overarching aim is to enhance patient outcomes, lessen the disease burden, and elevate the quality of life for those affected. Ongoing research and clinical trials in this area continue to offer promising opportunities for refining treatment strategies and improving patient prognosis.
    Review • Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    3ms
    Clinical features and long-term outcomes of pediatric patients with de novo acute myeloid leukemia in China with or without specific gene abnormalities: a cohort study of patients treated with BCH-AML 2005. (PubMed, Hematology)
    Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP214 (Nucleoporin 214) • CBFB (Core-Binding Factor Subunit Beta 2) • DEK (DEK Proto-Oncogene)
    |
    FLT3-ITD mutation • KIT mutation • KMT2A rearrangement • MLL rearrangement • DEK-NUP214 rearrangement
    3ms
    A simplified and robust risk stratification model for stem cell transplantation in pediatric acute myeloid leukemia. (PubMed, Cell Rep Med)
    Moreover, by incorporating the FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) allelic ratio, the pAML SCT model is refined, enhancing its ability to effectively select suitable candidates. We develop a simple and robust risk stratification model for pAML patients undergoing SCT, to aid in risk stratification and inform pretransplant decision-making at CR1 stage.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    4ms
    Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. (PubMed, Lancet Oncol)
    Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid leukaemia. Phase 2 assessment of ziftomenib combination therapy in the upfront and relapsed or refractory setting is ongoing.
    P1 data • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement • MLL mutation
    |
    ziftomenib (KO-539)
    4ms
    Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia. (PubMed, Hemasphere)
    Human KMT2A-r AML cells could be pharmacologically sensitized to NKG2D-CAR T cells by treatment with the histone deacetylase inhibitor LBH589 (panobinostat) which caused upregulation of NKG2D-ligand levels...Finally, the results were validated and extended to acute leukemia in infancy. Combined, activating mutations induced mutation-specific changes in the epigenetic landscape, leading to changes in transcriptional programs orchestrated by specific transcription factor networks.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • NKG2D (killer cell lectin like receptor K1)
    |
    RAS mutation • KMT2A rearrangement • MLL rearrangement • NRAS G12D • NRAS G12 • FLT3 N676K • MLL mutation • KMT2A expression
    |
    Farydak (panobinostat)
    4ms
    Pitfalls in Diagnosis: JMML versus KMT2A Rearranged Juvenile AML. (PubMed, Case Rep Hematol)
    This case highlights the challenges of diagnosing KMT2A-rearranged monocytic AML and the importance of careful morphological assessment in partnership with cytogenetic and molecular diagnostics to distinguish between KMT2A-rearranged AML and JMML. Moreover, the emerging role of molecular monitoring in AML is highlighted.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    4ms
    Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy. (PubMed, Blood Adv)
    Gilteritinib is the current standard of care for relapsed or refractory FLT3-mutated AML in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or non-intensive chemotherapy with venetoclax) are uncertain. Twenty patients received gilteritinib as first salvage having progressed following first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials but outcomes remain suboptimal, with more effective strategies needed.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    FLT3 mutation • RUNX1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • Xospata (gilteritinib) • Rydapt (midostaurin)
    4ms
    Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study. (PubMed, Leukemia)
    Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.
    Journal
    |
    RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
    |
    KMT2A rearrangement • MLL rearrangement
    8ms
    Immune escape of B-cell lymphoblastic leukemic cells through a lineage switch to acute myeloid leukemia. (PubMed, Leuk Lymphoma)
    Forty patients (37.7%) received lineage-specific immunotherapy. Our findings suggest that the prevalence of KMT2A rearrangements together with the lineage-specific immunotherapy may trigger LS, which supports the thesis of the existence of leukemia stem cells that are capable of lymphoid or myeloid differentiation.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    8ms
    Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia. (PubMed, Cancers (Basel))
    KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • KMT2A-PTD
    9ms
    Role of Interphase FISH Assay on Air-Dried Smears in Identifying Specific Structural Chromosomal Abnormalities among Pediatric Patients with Acute Leukemias. (PubMed, Indian J Hematol Blood Transfus)
    It can be considered an efficient alternative to conventional karyotyping for  identifying specific SCA of interest in under-resourced laboratories. The online version contains supplementary material available at 10.1007/s12288-023-01699-2.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
    |
    KMT2A rearrangement • MLL rearrangement
    9ms
    Outcomes and genetic dynamics of acute myeloid leukemia at first relapse. (PubMed, Haematologica)
    Complex karyotype (hazard ratio &lsqb;HR] = 2.14, P < 0.001), a KMT2A rearrangement (HR = 3.52, P = 0.011), time in remission < 12 months (HR = 1.71, P = 0.011), and an elevated white blood cell count at relapse (HR = 2.38, P = 0.005) were independent risk factors for OS duration. More effective frontline and maintenance therapies are warranted to prevent rAML.
    Journal
    |
    TP53 (Tumor protein P53) • KMT2A (Lysine Methyltransferase 2A)
    |
    TP53 mutation • KMT2A rearrangement • MLL rearrangement
    9ms
    Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. (PubMed, Pediatr Blood Cancer)
    EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    Mylotarg (gemtuzumab ozogamicin)
    9ms
    Characteristics and treatment of acute myeloid neoplasms with cutaneous involvement in infants up to 6 months of age: A retrospective study. (PubMed, Pediatr Blood Cancer)
    In the largest cohort to date, our study describes the characteristics of infants with cutaneous involvement of myeloid neoplasms including cytomolecular findings and survival rates. Further prospective biologic and clinical studies of these infants with myeloid neoplasms will be required to individualize therapy for this rare patient population.
    Retrospective data • Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement • MLL mutation
    9ms
    Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. (PubMed, Cancers (Basel))
    The impact of revumenib on KMT2Ar or NPM1c AML cells was significantly enhanced when combined with tamibarotene, demonstrating synergistic differentiation or apoptosis initiation. These findings propose promising strategies for relapsed/refractory AML patients with defined molecular characteristics.
    Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • RARA (Retinoic Acid Receptor Alpha) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Revuforj (revumenib) • Amnolake (tamibarotene)
    10ms
    Terminal deoxynucleotidyl transferase expression in different subtypes of childhood B-cell acute lymphoblastic leukemia. (PubMed, Pathol Res Pract)
    Moreover, several aberrant markers, such as CD2, CD56, CD7, and CD117, were rarely expressed in the B-ALL samples, and if expressed, they were enriched in specific genetic subtypes. The results of this study indicate that immunophenotypic features are correlated with specific genetic subtypes of childhood B-ALL.
    Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • NCAM1 (Neural cell adhesion molecule 1) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • MEF2D (Myocyte Enhancer Factor 2D)
    |
    KMT2A rearrangement • MLL rearrangement
    10ms
    Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia (clinicaltrials.gov)
    P3, N=160, Recruiting, Princess Maxima Center for Pediatric Oncology | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement
    |
    Blincyto (blinatumomab)
    10ms
    Extracellular matrix protein 1 (ECM1) is a potential biomarker in B cell acute lymphoblastic leukemia. (PubMed, Clin Exp Med)
    After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL.Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry &lsqb;ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn .
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)
    |
    KMT2A rearrangement • MLL rearrangement • IKZF1 deletion • ABL1 deletion
    10ms
    Raman spectroscopy can recognize the KMT2A rearrangement as a distinct subtype of leukemia. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc)
    This is the first time that a particular group of leukemic cells has been identified in a label-free way. The identified biomarker can be used as a screening method in diagnostic laboratories or non-reference medical centers.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
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    KMT2A rearrangement • MLL rearrangement
    10ms
    Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia. (PubMed, Ann Hematol)
    We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.
    Journal • Minimal residual disease
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    ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
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    KMT2A rearrangement • MLL rearrangement
    10ms
    Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors (clinicaltrials.gov)
    P2, N=9, Terminated, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Mar 2024; Low accrual
    Trial completion date • Trial termination • Trial primary completion date
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • NUP214 (Nucleoporin 214) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene)
    |
    TP53 mutation • RUNX1 mutation • KMT2A rearrangement • IKZF1 mutation • MLL mutation • Chr t(9;11)
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    Rituxan (rituximab) • cyclophosphamide • clofarabine • melphalan • fludarabine IV • thiotepa • busulfan
    11ms
    Enhanced potency of immunotherapy against B-cell precursor acute lymphoblastic leukemia by combination of an Fc-engineered CD19 antibody and CD47 blockade. (PubMed, Hemasphere)
    Our findings support that the efficacy of Fc-engineered CD19 antibodies may be substantially enhanced by a combination with CD47 blockade. This suggests that the combination may be a promising therapy option for BCP-ALL, especially in relapsed patients and/or patients refractory to CD19-directed therapy.
    Journal • IO biomarker
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    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    |
    KMT2A rearrangement • MLL rearrangement • CD19 expression • KMT2A-AFF1 fusion
    11ms
    Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey. (PubMed, Leuk Lymphoma)
    Outcome was particularly poor in Ph + trALL compared to Ph+ de novo ALL, which seemed to be mitigated by allogeneic stem cell transplantation. Our findings further define trALL as a distinct entity but highlight the need for further molecular genome sequencing of somatic and germline variants to advance our understanding of trALL.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • KMT2D (Lysine Methyltransferase 2D)
    |
    TP53 mutation • KRAS mutation • DNMT3A mutation • KMT2A rearrangement • KMT2D mutation • MLL rearrangement
    11ms
    A Study of BN104 in the Treatment of Acute Leukemia (clinicaltrials.gov)
    P1/2, N=90, Recruiting, BioNova Pharmaceuticals (Shanghai) LTD. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement • KMT2A mutation • MLL mutation
    11ms
    Mapping AML heterogeneity - multi-cohort transcriptomic analysis identifies novel clusters and divergent ex-vivo drug responses. (PubMed, Leukemia)
    In conclusion, our findings underscore the importance of transcriptomics in AML subtyping and offer a basis for future research and personalised treatment strategies. Our transcriptomic compendium is publicly available and we supply an R package to project clusters to new transcriptomic studies.
    Preclinical • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement • CEBPA mutation
    12ms
    Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation. (PubMed, Oncol Ther)
    Recent phase 1/2 clinical trials confirmed the efficacy of SNDX-5613 (revumenib) and KO-539 (ziftomenib) and their acceptable tolerability. Several small molecule menin inhibitors are currently being evaluated as a combination therapy with standard of care treatments. The current paper reviews the recent progress in exploring the inhibitors of menin-KMT2A interactions and their application prospects in the treatment of acute leukemias.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Revuforj (revumenib) • ziftomenib (KO-539)