1,715 results match your criteria kmt2a gene

Outcomes of Acute Lymphoblastic Leukemia with KMT2A (MLL) rearrangement - The MD Anderson Experience.

Blood Adv 2021 Sep 15. Epub 2021 Sep 15.

University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States.

Acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23) - KMT2A-AFF1 is associated with a poor prognosis. The impact of KMT2A rearrangements other than t(4;11) is uncertain and the benefit of allogeneic stem cell transplant (HSCT) is unclear. We reviewed adult patients with ALL treated at our institution from 1984 to 2019 and identified 50/1102 (5%) with KMT2A rearrangement: 42 (84%) with t(4;11)/KMT2A-AFF1 and 8 (16%) with other gene partners. Read More

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September 2021

Hematopoietic stem cell transplantation for infants with high-risk KMT2A gene rearranged acute lymphoblastic leukemia.

Blood Adv 2021 Sep 9. Epub 2021 Sep 9.

National Center for Child Health and Development, Tokyo, Japan.

The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential of acute and late toxicities. In the Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to the patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Read More

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September 2021

[Acute leukemia of infants and neonates].

Mariko Eguchi

Rinsho Ketsueki 2021 ;62(8):1308-1318

Department of Pediatrics, Ehime University Graduate School of Medicine.

Leukemias diagnosed in <1-year-old infants generally have an aggressive clinical nature and unique biological characteristics. Acute lymphoblastic leukemia (ALL) in infants is still intractable and difficult to treat as compared with other pediatric ALLs, for which considerable progress in treatment outcomes has been recently achieved. Infant leukemia cells frequently carry chromosome translocations involving the 11q23 locus, resulting in the rearrangement and fusion of the KMT2A (MLL) gene. Read More

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September 2021

Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic Mutations Based on a Multi-Gene Panel and Nomogram Model.

Front Oncol 2021 17;11:706935. Epub 2021 Aug 17.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Background: Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic (bi) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.

Methods: In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Read More

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Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann-Steiner syndrome.

Mol Genet Genomic Med 2021 Sep 1:e1798. Epub 2021 Sep 1.

Precision Medical Laboratory, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

Background: Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. WSS patients exhibit great phenotypic heterogeneities. Some variants in KMT2A (MLL) gene have been identified as the cause of WSS. Read More

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September 2021

, and Are Novel Partner Genes in Childhood Acute Leukemia.

Biomedicines 2021 Jul 30;9(8). Epub 2021 Jul 30.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia.

Chromosomal rearrangements of the human / gene are associated with acute leukemias, especially in infants. is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients' outcome. Read More

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Assessing acute myeloid leukemia susceptibility in rearrangement-driven patients by DNA breakage at topoisomerase II and CCCTC-binding factor/cohesin binding sites.

Genes Chromosomes Cancer 2021 Aug 18. Epub 2021 Aug 18.

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

An initiating DNA double strand break (DSB) event precedes the formation of cancer-driven chromosomal abnormalities, such as gene rearrangements. Therefore, measuring DNA breaks at rearrangement-participating regions can provide a unique tool to identify and characterize susceptible individuals. Here, we developed a highly sensitive and low-input DNA break mapping method, the first of its kind for patient samples. Read More

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BETting on a Transcriptional Deficit as the Main Cause for Cornelia de Lange Syndrome.

Front Mol Biosci 2021 27;8:709232. Epub 2021 Jul 27.

Andalusian Centre for Molecular Biology and Regenerative Medicine-CABIMER, CSIC-Universidad de Sevilla-Universidad Pablo de Olavide, Seville, Spain.

Cornelia de Lange Syndrome (CdLS) is a human developmental syndrome with complex multisystem phenotypic features. It has been traditionally considered a cohesinopathy together with other phenotypically related diseases because of their association with mutations in subunits of the cohesin complex. Despite some overlap, the clinical manifestations of cohesinopathies vary considerably and, although their precise molecular mechanisms are not well defined yet, the potential pathomechanisms underlying these diverse developmental defects have been theoretically linked to alterations of the cohesin complex function. Read More

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The Application of Targeted RNA Sequencing for KMT2A-Partial Tandem Duplication Identification and Integrated Analysis of Molecular Characterization in Acute Myeloid Leukemia.

J Mol Diagn 2021 Aug 10. Epub 2021 Aug 10.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

The partial tandem duplication of histone-lysine N-methyltransferase 2A (KMT2A-PTD) is an important genetic alteration in acute myeloid leukemia (AML) and is associated with poor clinical outcome. Accurate and rapid detection of KMT2A-PTD is important for outcome prediction and clinical management, but next-generation sequencing-based quantitative research is still lacking. In this study, we developed a targeted RNA-based next-generation sequencing panel, together with single primer enrichment and unique molecular identifiers, to identify KMT2A-PTD as well as AML-related gene fusions and other driver mutations. Read More

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KMT2A-ARHGEF12, a therapy related fusion with poor prognosis.

Mol Biol Rep 2021 Aug 12. Epub 2021 Aug 12.

Department of Laboratory Medicine, Hemato-Oncologic Cytogenetics, Centre Hospitalier de Versailles, 2, rue JL Forain, 78150, Le Chesnay, France.

Background: The detection of KMT2A gene rearrangements have an important impact on the prognosis and management of acute leukemias. These alterations most commonly involve reciprocal translocations at specific breakpoint regions within KMT2A. To date, more than 100 translocation partner genes of KMT2A have been identified, with different effects on risk stratification. Read More

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[Leukemogenic pathway of infant leukemia with MLL fusion].

Mariko Eguchi

Rinsho Ketsueki 2021 ;62(7):809-819

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon.

Acute lymphoblastic leukemia (ALL) in infants remains an intractable and difficult-to-treat leukemia as compared to other pediatric ALLs, for which considerable progress has been achieved in terms of treatment outcomes in recent years. The leukemic cells in infants with ALL frequently carry chromosome translocations involving 11q23, resulting in the rearrangement and fusion of the MLL (KMT2A) gene. Among many MLL fusion genes, MLL-AF4 (KMT2A-AFF1) fusion is characteristically observed in infants with ALL, representing a hallmark of poor prognosis. Read More

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Mature B cell acute lymphoblastic leukaemia with KMT2A-MLLT3 transcripts in children: three case reports and literature reviews.

Orphanet J Rare Dis 2021 07 30;16(1):331. Epub 2021 Jul 30.

Division of Haematology and Oncology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People's Republic of China.

Background: Mature B cell acute lymphoblastic leukaemia (BAL) is characterised by French-American-British (FAB)-L3 morphology and the presence of surface immunoglobulin (sIgM) light chain restriction. BAL is also considered as the leukaemic phase of Burkitt lymphoma (BL), in which t (8; 14) (q24; q32) or its variants are related to the myelocytomatosis oncogene (MYC) rearrangement (MYCr) is usually present. However, BAL with lysine methyltransferase 2A (KMT2A, previously called Mixed lineage leukaemia, MLL) gene rearrangement (KMT2Ar, previously called MLLr) is rare. Read More

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Acute lymphoblastic leukemia in infants: a quarter century of nationwide efforts in Japan.

Pediatr Int 2021 Jul 29. Epub 2021 Jul 29.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.

Acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement (KMT2A-r) in infants is a biologically and clinically unique disease and one of the most difficult-to-cure forms of pediatric leukemia. Continuing nationwide efforts by conducting multicenter clinical trials have been carried out in Japan since the mid-1990s by introducing allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, which led to a modest improvement in outcome of infants with KMT2A-r ALL. Because of the emerging evidence that HSCT does not benefit every infant with KMT2A-r ALL, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) trial MLL-10 introduced risk stratification using age and presence of CNS leukemia and introduced intensive chemotherapy including high-dose cytarabine in early consolidation; indication of HSCT was restricted to the patients with high-risk features. Read More

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Loss of KMT2C reprograms the epigenomic landscape in hPSCs resulting in NODAL overexpression and a failure of hemogenic endothelium specification.

Epigenetics 2021 Jul 24:1-19. Epub 2021 Jul 24.

Department of Pediatrics, Division of Pediatric Hematology and Oncology, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States.

Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. Read More

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Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma.

J Immunother Cancer 2021 Jul;9(7)

Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA

Background: Tumor-infiltrating CD8 T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion. Read More

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Identification of KMT2A-ARHGEF12 fusion in a child with a high-grade B-cell lymphoma.

Cancer Genet 2021 Jun 27;258-259:23-26. Epub 2021 Jun 27.

ARUP Laboratories, Salt Lake City, UT, United States; Department of Pathology, University of Utah, Salt Lake City, UT, United States. Electronic address:

Rearrangements involving KMT2A are common in de novo and therapy-related acute myeloid and lymphoblastic leukemias. There is a diverse recombinome associated with KMT2A involving at least 135 partner genes, with more being discovered due to advances in molecular genetic diagnostics. KMT2A-ARHGEF12 fusion has only rarely been reported, in five cases of acute leukemia and a single case of high-grade B-cell lymphoma. Read More

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Novel MLL/KMT2A-MON2 fusion in a child with therapy-related acute myeloid leukemia after treatment for acute promyelocytic leukemia.

Mol Carcinog 2021 Jul 8. Epub 2021 Jul 8.

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, P.R China.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), which is characterized by the reciprocal t (15;17) (q24; q21) translocation, resulting in PML-RARA gene fusion. Therapy-related AML (t-AML) is a serious complication after cytotoxic and/or radiation therapy in many malignant diseases. In this report, MLL/KMT2A-MON2, with balanced chromosomal translocation t (11;12) (q23; q14), was identified as a novel fusion in a child transformed to t-AML after successful treatment of APL. Read More

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Novel germline mutation KMT2A G3131S confers genetic susceptibility to familial myeloproliferative neoplasms.

Ann Hematol 2021 Sep 6;100(9):2229-2240. Epub 2021 Jul 6.

Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.

The current study analyzed the clinical and genetic characteristics of a family with familial myeloproliferative neoplasms (MPNs). Whole-exome sequencing was conducted, and a germline heterozygous mutation in lysine methyltransferase 2A (KMT2A, also known as MLL1), G3131S (c.9391G > A, p. Read More

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September 2021

Identification and Characterization of Non-Coding RNAs in Thymoma.

Med Sci Monit 2021 Jul 5;27:e929727. Epub 2021 Jul 5.

Second Department of Thoracic Surgery, Linyi Cancer Hospital, Linyi, Shandong, China (mainland).

BACKGROUND Thymoma is the most common tumor of the anterior mediastinum, and can be caused by infrequent malignancies arising from the epithelial cells of the thymus. Unfortunately, blood-based diagnostic markers are not currently available. High-throughput sequencing technologies, such as RNA-seq with next-generation sequencing, have facilitated the detection and characterization of both coding and non-coding RNAs (ncRNAs), which play significant roles in genomic regulation, transcriptional and post-transcriptional regulation, and imprinting and epigenetic modification. Read More

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Hypodiploidy in a pediatric patient of T-cell acute lymphoblastic leukemia: a case report.

BMC Med Genomics 2021 Jul 3;14(1):178. Epub 2021 Jul 3.

Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Gębali 6, 20-093, Lublin, Poland.

Background: T-cell acute lymphoblastic leukemia is a subtype of acute lymphoblastic leukemia, one of the most common childhood neoplasms. Hypodiploidy is a chromosome abnormality with fewer than 45 chromosomes and is associated with unsatisfactory clinical outcomes in acute lymphoblastic leukemia.

Case Presentation: We report clinical and genetic findings of a 14-year-old male with T-cell acute lymphoblastic leukemia with low-hypodiploidy. Read More

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Irinotecan Induces Disease Remission in Xenograft Mouse Models of Pediatric -Rearranged Acute Lymphoblastic Leukemia.

Biomedicines 2021 Jun 23;9(7). Epub 2021 Jun 23.

Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.

Acute lymphoblastic leukemia (ALL) in infants (<1 year of age) remains one of the most aggressive types of childhood hematologic malignancy. The majority (~80%) of infant ALL cases are characterized by chromosomal translocations involving the (or ) gene, which confer highly dismal prognoses on current combination chemotherapeutic regimens. Hence, more adequate therapeutic strategies are urgently needed. Read More

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DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML).

Genes (Basel) 2021 06 10;12(6). Epub 2021 Jun 10.

Department of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University, 752 37 Uppsala, Sweden.

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. Read More

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Therapeutic implications of menin inhibition in acute leukemias.

Leukemia 2021 09 15;35(9):2482-2495. Epub 2021 Jun 15.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Menin inhibitors are novel targeted agents currently in clinical development for the treatment of genetically defined subsets of acute leukemia. Menin has a tumor suppressor function in endocrine glands. Germline mutations in the gene encoding menin cause the multiple endocrine neoplasia type 1 (MEN1) syndrome, a hereditary condition associated with tumors of the endocrine glands. Read More

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September 2021

Novel combined variants of WT1 and TET2 in a refractory and recurrent AML patient.

BMC Med Genomics 2021 Jun 13;14(1):158. Epub 2021 Jun 13.

Department of Hematology, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Beijing, 100053, People's Republic of China.

Background: Somatic mutations in Wilms' tumor 1 (WT1) and tet methylcytosine dioxygenase 2 (TET2) genes were separately perceived as contributors to hematopoietic disorders and usually thought to have a mutually exclusive effect in acute myeloid leukemia (AML). However, we found novel WT1 and TET2 variants persistently co-existed in a refractory and recurrent AML patient with t(9;11)(p21.3;q23. Read More

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Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML.

Cell Death Discov 2021 Jun 10;7(1):137. Epub 2021 Jun 10.

Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Over the last 50 years, there has been a steady improvement in the treatment outcome of acute myeloid leukemia (AML). However, median survival in the elderly is still poor due to intolerance to intensive chemotherapy and higher numbers of patients with adverse cytogenetics. Fadraciclib (CYC065), a novel cyclin-dependent kinase (CDK) 2/9 inhibitor, has preclinical efficacy in AML. Read More

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Discovery of as a Potent and Orally Bioavailable Inhibitor of the WDR5-Mixed Lineage Leukemia 1 Protein-Protein Interaction for the Treatment of MLL Fusion Leukemia.

J Med Chem 2021 06 9;64(12):8221-8245. Epub 2021 Jun 9.

Jiangsu Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

WD repeat-containing protein 5 (WDR5) is essential for the stability and methyltransferase activity of the mixed lineage leukemia 1 (MLL1) complex. Dysregulation of the gene is associated with human acute leukemias, and the direct disruption of the WDR5-MLL1 protein-protein interaction (PPI) is emerging as an alternative strategy for MLL-rearranged cancers. Here, we represent a new aniline pyrimidine scaffold for WDR5-MLL1 inhibitors. Read More

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[A case of Wiedemann-Steiner syndrome caused by a novel variation of the KMT2A gene].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):516-518

Department of Endorinology, the Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.

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A KMT2A-AFF1 gene regulatory network highlights the role of core transcription factors and reveals the regulatory logic of key downstream target genes.

Genome Res 2021 Jun 4. Epub 2021 Jun 4.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, United Kingdom.

Regulatory interactions mediated by transcription factors (TFs) make up complex networks that control cellular behavior. Fully understanding these gene regulatory networks (GRNs) offers greater insight into the consequences of disease-causing perturbations than can be achieved by studying single TF binding events in isolation. Chromosomal translocations of the () gene produce KMT2A fusion proteins such as KMT2A-AFF1 (previously MLL-AF4), causing poor prognosis acute lymphoblastic leukemias (ALLs) that sometimes relapse as acute myeloid leukemias (AMLs). Read More

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plays critical roles in disease progression and response to cytarabine in AML.

Oncol Rep 2021 Jul 3;46(1). Epub 2021 Jun 3.

Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan, R.O.C.

Lysine methyltransferase 2A (, also known as ) translocations (‑t) are frequently associated with mutations in pathway genes in acute myeloid leukemia (AML). Previous findings with a mouse model showed that cooperation of with tyrosine‑protein phosphatase non‑receptor type 11  accelerated leukemia development, but increased cytarabine (Ara‑C) sensitivity of leukemia cells. To identify the genes responsible for reduced survival and Ara‑C resistance, transcriptomic profiling between six pairs of mouse leukemia cells harboring activating and wild‑type or was compared. Read More

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Biochemical perspectives on targeting KMT2 methyltransferases in cancer.

Trends Pharmacol Sci 2021 08 30;42(8):688-699. Epub 2021 May 30.

Bioscience, Oncology R&D, AstraZeneca, Waltham, MA 02451, USA.

KMT2 methyltransferases are important regulators of gene transcription through the methylation of histone H3 lysine 4 at promoter and enhancer regions. They reside in large, multisubunit protein complexes, which not only regulate their catalytic activities but also mediate their interactions with chromatin. The KMT2 family was initially associated with cancer due to the discovery of KMT2A translocations in mixed-lineage leukemia (MLL). Read More

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