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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
    1d
    The Menin story in acute myeloid leukaemia-The road to success. (PubMed, Br J Haematol)
    Other HOX and MEIS1 expressing leukaemias may also be sensitive to Menin inhibition. Following the encouraging results as monotherapy in refractory and relapsed AML, the combination of Menin inhibitors with chemotherapeutic agents and other targeted drugs is being investigated clinically.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1) • PBX3 (PBX Homeobox 3)
    |
    NPM1 mutation • MLL rearrangement • MLL mutation • MLL fusion
    2d
    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
    6d
    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
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    TP53 (Tumor protein P53) • KMT2A (Lysine Methyltransferase 2A)
    |
    TP53 mutation • KMT2A rearrangement • MLL rearrangement
    6d
    The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia. (PubMed, Cell Death Discov)
    EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
    |
    MLL rearrangement • MLL rearrangement
    8d
    Multilineage involvement in KMT2A-rearranged B acute lymphoblastic leukaemia: cell-of-origin, biology, and clinical implications. (PubMed, Histopathology)
    In summary, multilineage involvement is common in both BCR::ABL1-rearranged and KMT2A-rearranged B-ALL, which should be taken into consideration when interpreting the disease burden during the clinical course.
    Journal
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    ABL1 (ABL proto-oncogene 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement • ABL1 fusion
    9d
    Ribosome subunit attrition and activation of the p53-MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition. (PubMed, Elife)
    We also show that WINi are synergistic with agents including venetoclax and BET-bromodomain inhibitors. Together, these studies reinforce the concept that WINi are a novel type of ribosome-directed anticancer therapy and provide a resource to support their clinical implementation in MLLr leukemias and other malignancies.
    Journal
    |
    MDM4 (The mouse double minute 4) • WDR5 (WD Repeat Domain 5)
    |
    MLL rearrangement
    |
    Venclexta (venetoclax)
    11d
    The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia. (PubMed, Oncogene)
    In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.
    Journal
    |
    DOT1L (DOT1 Like Histone Lysine Methyltransferase)
    |
    MLL rearrangement
    13d
    A rare KMT2A::CBL transcript in an acute monoblastic leukemia patient with an unfavorable outcome. (PubMed, Mol Biol Rep)
    This report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.
    Journal
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    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    14d
    A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia. (PubMed, Hematol Rep)
    To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.
    Review • Journal
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • MEIS1 (Meis Homeobox 1)
    |
    NPM1 mutation • MLL rearrangement • KMT2A expression
    |
    revumenib (SNDX-5613) • ziftomenib (KO-539)
    16d
    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)
    16d
    Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers (clinicaltrials.gov)
    P2, N=10, Recruiting, Fred Hutchinson Cancer Center | Trial primary completion date: Dec 2024 --> Jun 2024
    Trial primary completion date
    |
    MLL rearrangement • MLL rearrangement
    |
    cyclophosphamide • fludarabine IV • thiotepa • dilanubicel (DVX101)
    20d
    KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia. (PubMed, Leukemia)
    No abstract available
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • KMT2A (Lysine Methyltransferase 2A)
    |
    KRAS mutation • KRAS G12 • MLL rearrangement
    21d
    Infant Acute Lymphoblastic Leukemia-New Therapeutic Opportunities. (PubMed, Int J Mol Sci)
    Progress in the development of molecularly targeted therapies and immunotherapy presents exciting opportunities for potential improvement. This comprehensive review synthesizes the current literature on the epidemiology, clinical presentation, molecular genetics, and therapeutic approaches specific to ALL in the infant population.
    Review • Journal
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    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    22d
    Optimized Cytogenetic Risk-Group Stratification of KMT2A-Rearranged Pediatric Acute Myeloid Leukemia. (PubMed, Blood Adv)
    We provide evidence to incorporate the five adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcome, and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • SEPTIN6 (Septin 6) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    MLL rearrangement • MLL fusion
    23d
    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
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    KMT2A (Lysine Methyltransferase 2A)
    |
    KMT2A rearrangement • MLL rearrangement • MLL mutation
    25d
    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
    |
    revumenib (SNDX-5613) • Amnolake (tamibarotene)
    26d
    Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL. (PubMed, Blood Adv)
    This trial was registered at www.clinicaltrials.gov as no. NCT01564784.
    Journal
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    |
    Besponsa (inotuzumab ozogamicin)
    29d
    Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • 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) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation
    |
    cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
    1m
    AALL1621: Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=80, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting
    Enrollment open
    |
    KMT2A (Lysine Methyltransferase 2A) • CD22 (CD22 Molecule)
    |
    MLL rearrangement • CD22 expression
    |
    cytarabine • cyclophosphamide • methotrexate • Besponsa (inotuzumab ozogamicin) • vincristine • leucovorin calcium • Oncaspar liquid (pegaspargase) • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)
    1m
    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
    1m
    Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia. (PubMed, Curr Opin Genet Dev)
    Recent work has shown that the MLL-AF4 fusion protein drives aberrant enhancer activity at key oncogenes in ALL, dependent on the continued presence of MLL-AF4 complex components. As well as providing some general insights into enhancer function, these observations may also provide an explanation for transcriptional heterogeneity observed in MLLr patients.
    Review • Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement • MLL-AF4 fusion
    1m
    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)
    1m
    Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases (clinicaltrials.gov)
    P2, N=54, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KMT2A (Lysine Methyltransferase 2A) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
    |
    MLL rearrangement • MLL rearrangement
    |
    cyclophosphamide • fludarabine IV • thiotepa
    1m
    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
    1m
    A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia. (PubMed, Leukemia)
    Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells' ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.
    Journal
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    KMT2A (Lysine Methyltransferase 2A) • IGF2 (Insulin-like growth factor 2)
    |
    MLL rearrangement • KMT2A expression
    1m
    Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia (PubMed, Zhonghua Er Ke Za Zhi)
    The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.
    Journal • Minimal residual disease
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    RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
    |
    MLL rearrangement
    2ms
    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)
    |
    KMT2A rearrangement • MLL rearrangement
    2ms
    Measurable residual disease quantification in adult patients with KMT2A-rearranged acute lymphoblastic leukemia. (PubMed, Leukemia)
    No abstract available
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    2ms
    Palbociclib and chemotherapy followed by blinatumomab consolidation to CAR-T cell therapy in KMT2A-rearranged, therapy-related acute lymphoblastic leukemia. (PubMed, Pediatr Blood Cancer)
    No abstract available
    Journal • CAR T-Cell Therapy
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    |
    Ibrance (palbociclib) • Blincyto (blinatumomab)
    2ms
    A Study of SNDX-5613 in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia (clinicaltrials.gov)
    P2, N=78, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    |
    cytarabine • methotrexate • vincristine • revumenib (SNDX-5613) • fludarabine IV • Asparlas (calaspargase pegol-mknl) • Starasid (cytarabine ocfosfate)
    2ms
    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
    |
    ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6)
    |
    KMT2A rearrangement • MLL rearrangement
    2ms
    Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov)
    P1, N=28, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027
    Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • MLL rearrangement • FLT3 wild-type • MLL mutation
    |
    daunorubicin • revumenib (SNDX-5613) • Starasid (cytarabine ocfosfate)
    2ms
    Regulation of HOX gene expression in AML. (PubMed, Blood Cancer J)
    Recent identification of the menin-MLL interaction as a critical vulnerability of HOX-dependent AML has fueled the development of menin inhibitors that are clinically active in NPM1 and MLL rearranged AML despite inconsistent suppression of the HOX locus. Insights into context-specific regulation of HOX in AML may provide a solid foundation for targeting this common vulnerability across several major AML subtypes.
    Review • Journal
    |
    NPM1 (Nucleophosmin 1) • FOXM1 (Forkhead Box M1)
    |
    NPM1 mutation • MLL rearrangement
    2ms
    Further validation of poor prognosis for pediatric KMT2A-rearranged leukemia and the need for rapid integration of targeted therapies for these patients. (PubMed, Transl Pediatr)
    No abstract available
    Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement
    2ms
    Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL-mediated leukemia. (PubMed, Blood Adv)
    In a public database, high BAHCC1 expression was associated with a poor prognosis in pediatric AML, in which BAHCC1 expression was significantly lower in MLL-AF9-AML than in other MLL-fusion-AML. These findings shed light on the distinct immortalization potential of HSPCs and suggest a novel MLL-fusion-Bahcc1 axis, which may lead to development of molecular targeted therapy against MLL-fusion-mediated leukemia.
    Preclinical • Journal
    |
    CD48 (CD48 Molecule) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C)
    |
    MLL rearrangement • MLL fusion
    2ms
    Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia (clinicaltrials.gov)
    P2, N=70, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • CD8 (cluster of differentiation 8) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1)
    |
    MLL rearrangement
    |
    cyclophosphamide • fludarabine IV
    2ms
    Detection of KMT2A-PTDs and KMT2A fusions using next generation sequencing (AACR 2024)
    We characterize the KMT2A fusions present in myeloid malignant samples. We also describe the abundance of KMT2A PTDs in both healthy donor and myeloid samples, with myeloid cases showing significantly higher PTD read counts. KMT2A PTD read count >2000 is present only in malignant samples but not in healthy donors.
    Next-generation sequencing
    |
    KMT2A (Lysine Methyltransferase 2A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
    |
    MLL rearrangement • MLL rearrangement • KMT2A-PTD • MLL fusion
    |
    Oncomine Myeloid Assay GX
    2ms
    Tocilizumab for the Prevention of Graft Versus Host Disease After Cord Blood Transplantation (clinicaltrials.gov)
    P2, N=46, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement • MLL rearrangement
    |
    Actemra IV (tocilizumab) • Neupogen (filgrastim)
    2ms
    BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor. (PubMed, Blood)
    Compared to each drug, co-treatment with FHD-286 and BETi, MI, decitabine or venetoclax significantly reduced AML burden and improved survival, without inducing significant toxicity. These findings highlight the FHD-286-based combinations as promising therapy of AML with MLL1r or mtNPM1.
    Preclinical • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    NPM1 mutation • MLL rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • decitabine • FHD-286
    2ms
    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
    |
    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
    2ms
    High-dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study. (PubMed, Br J Haematol)
    Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics...The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower-risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady-state concentrations within the optimal range.
    PK/PD data • Journal
    |
    KMT2A (Lysine Methyltransferase 2A)
    |
    MLL rearrangement • MLL rearrangement
    |
    dasatinib • methotrexate
    3ms
    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
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    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)
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    TP53 mutation • KRAS mutation • DNMT3A mutation • KMT2A rearrangement • KMT2D mutation • MLL rearrangement