t(8;19)(p11;q13) KAT6A/?

2003-12-01   Jacques Boyer  

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology

Disease

Acute myelomonocytic or monocytic leukaemia (M4, M5a, M5b) associated with erythrophagocytosis by blasts noted to various degree.

Epidemiology

Rare

Cytology

Morphology feature observed in AML with t(8;16).

Prognosis

probably poor

Cytogenetics

Cytogenetics morphological

t(8;19) (p11;q13) is a variant of t(8;16) (p11;p13)

Additional anomalies

Two cases :
  • 46,XX,t(8;19)(p11;q13.2)/idem,-16,-16q+
  • 46,XX, t(8;19)(p11;q13) sole anomaly

    • Genes Involved and Proteins

    Gene name
    KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3
    Location
    8p11.21
    Note
    MOZ contains a LAP (Leukemia associated protein) zinc finger domain, a HAT domain (Histone acetyltransferase) and a acidic domain. Detection by FISH : YAC 176C9.
    Protein description
    ZNF220
    Monocytic leukemia zinc finger protein
    2004 amino acids and 225 kDa nuclear protein, with 2 LAP/PHD-type zinc fingers.
    MOZ is a histone acetyltransferase (HAT) and the founding member of the MYST family of HATs, a family that includes proteins involved in cell cycle regulation, chromatin remodeling and dosage compensation.
    MOZ plays an important role during hematopoiesis with his transcriptional coregulator activity.
    Gene name
    The partner of MOZ is unknown in this translocation.
    Location
    19q13

    Result of the Chromosomal Anomaly

    Note

    In the t(8 ;19) the fusion protein is unknown.

    Highly cited references

    Pubmed IDYearTitleCitations
    300690492018Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.57
    294638862019A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development.38
    301441322018Histone Lysine and Genomic Targets of Histone Acetyltransferases in Mammals.31
    290211352017Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24 Binding.27
    302455132019KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.24
    319570182020Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort.23
    291655782018Clues for Polygenic Inheritance of Pituitary Stalk Interruption Syndrome From Exome Sequencing in 20 Patients.22
    326612452020High-performance CRISPR-Cas12a genome editing for combinatorial genetic screening.20
    312730842019Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter.17
    320107792020Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.15
    306222872019NEAT1-TFE3 and KAT6A-TFE3 renal cell carcinomas, new members of MiT family translocation renal cell carcinoma.15
    331441182021Targeting post-translational histone modifying enzymes in glioblastoma.14
    311260022019Cardiogenesis impairment promoted by bisphenol A exposure is successfully counteracted by epigallocatechin gallate.12
    312985652019Adipose-Derived Stem/Stromal Cells Recapitulate Aging Biomarkers and Show Reduced Stem Cell Plasticity Affecting Their Adipogenic Differentiation Capacity.11
    298067012018Neonatal leukaemia.11
    331305152020The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology.8
    295463192018Lineage specification revealed by single-cell gene expression analysis in porcine preimplantation embryos.8
    334393822021Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.7
    335414082021KAT6A regulates stemness of aging bone marrow-derived mesenchymal stem cells through Nrf2/ARE signaling pathway.7
    334886792020Impaired Regulation of Histone Methylation and Acetylation Underlies Specific Neurodevelopmental Disorders.7
    318639002020Long non-coding RNA DANCR promotes colorectal tumor growth by binding to lysine acetyltransferase 6A.7
    320416412020Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum.6
    316394002019Alterations in Eukaryotic Elongation Factor complex proteins (EEF1s) in cancer and their implications in epigenetic regulation.6
    286362592017Variants in KAT6A and pituitary anomalies.6
    336727822021Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome.5
    320152332021Specific Genomic Alterations in High-Grade Pulmonary Neuroendocrine Tumours with Carcinoid Morphology.5
    326773742020Tripartite motif containing 24 regulates cell proliferation in colorectal cancer through YAP signaling.5
    298995042018A KAT6A variant in a family with autosomal dominantly inherited microcephaly and developmental delay.5
    301051182018Paroxysmal Movement Disorder and Epilepsy Caused by a De Novo Truncating Mutation in KAT6A.5
    299771512018The Kat in the HAT: The Histone Acetyl Transferase Kat6b (MYST4) Is Downregulated in Murine Macrophages in Response to LPS.5
    290449902018Transcriptome analysis for UVB-induced phototoxicity in mouse retina.5
    352479062022Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.4
    343926142021KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer.4
    330590742020Global retardation and hereditary spherocytosis associated with a novel deletion of chromosome 8p11.21 encompassing KAT6A and ANK1.4
    328774612020KAT6A amplifications are associated with shorter progression-free survival and overall survival in patients with endometrial serous carcinoma.4
    321624422020Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features.4
    312105922019Transcriptome analysis identifies key regulators and networks in Acute myeloid leukemia.4
    307592702019Acute myeloid leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP in adults.4
    307750472019A Novel De Novo Frameshift Mutation in KAT6A Identified by Whole Exome Sequencing.4
    339956582021KAT6A, a novel regulator of β-catenin, promotes tumorigenicity and chemoresistance in ovarian cancer by acetylating COP1.3
    334249372020Genetic Determinism Exists for the Global DNA Methylation Rate in Sheep.3
    313409332019MOZ directs the distal-less homeobox gene expression program during craniofacial development.3
    312922552019Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis.3
    280977922017FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of spontaneously remitting congenital acute myeloid leukemia with a normal karyotype.3
    333266532021Functional and clinical implications of genetic structure in 1686 Italian exomes.2
    310105892019Several genotypes, one phenotype: PIK3CA/AKT1 mutation-negative hidradenoma papilliferum show genetic lesions in other components of the signalling network.2
    304171382018New KAT6 inhibitors induce senescence and arrest cancer growth.2
    288711372018C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation.2
    346983402022Distinctive Flow Cytometric and Mutational Profile of Acute Myeloid Leukemia With t(8;16)(p11;p13) Translocation.1
    354037812022Epithelial-mesenchymal transition and cancer stem cells: A route to acquired cisplatin resistance through epigenetics in HNSCC.1
    348530792022KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.1
    348085022021KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP.1
    346316942021Novel Molecular Subtypes and Related Score Based on Histone Acetylation Modification in Renal Clear Cell Carcinoma.1
    342957912021A de novo heterozygous variant in KAT6A is associated with a newly named neurodevelopmental disorder Arboleda-Tham syndrome-a case report.1
    337395542021Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability.1
    335526462021A Novel Frameshift Mutation in KAT6A Is Associated with Pancraniosynostosis.1
    333189322020Diagnosis of Arboleda-Tham syndrome by whole genome sequencing in an Asian boy with severe developmental delay.1
    327798582020Rapidly progressing acute myeloid leukemia with KAT6A-LEUTX fusion in a newborn.1
    323579732020Concentration Dependence of the Unbound Partition Coefficient Kpuu and Its Application to Correct for Exposure-Related Discrepancies between Biochemical and Cellular Potency of KAT6A Inhibitors.1
    321184272020Discovery of Acylsulfonohydrazide-Derived Inhibitors of the Lysine Acetyltransferase, KAT6A, as Potent Senescence-Inducing Anti-Cancer Agents.1
    322090612020Clinicopathologic features and genomic analysis of pulmonary blastomatoid carcinosarcoma.1
    320649382020Action plan for hit identification (APHID): KAT6A as a case study.1
    319987762020Next-Generation Sequencing Panel Analysis of Clinically Relevant Mutations in Circulating Cell-Free DNA from Patients with Gestational Trophoblastic Neoplasia: A Pilot Study.1
    312565872019Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A.1
    359471262022MOZ is critical for the development of MOZ/MLL-fusion-induced leukemia through regulation of Hoxa9/Meis1 expression.0
    356797992022Epigenetic modifications control loss of adhesion and aggressiveness of cancer stem cells derived from head and neck squamous cell carcinoma with intrinsic resistance to cisplatin.0
    359578372022Early-Onset Diabetes Mellitus in Chromosome 8p11.2 Deletion Syndrome Combined With Becker Muscular Dystrophy - A Case Report.0
    358922682022Speech and language development and genotype-phenotype correlation in 49 individuals with KAT6A syndrome.0
    353322662022Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression.0
    359764742022miR-339-3p inhibits cell growth and epithelial-mesenchymal transition in nasopharyngeal carcinoma by modulating the KAT6A/TRIM24 axis.0
    355757892022Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma.0
    359122322022Genomic Features of Organ-Specific Metastases in Lung Adenocarcinoma.0
    357941582022Hsa-miR-143-3p inhibits Wnt-β-catenin and MAPK signaling in human corneal epithelial stem cells.0
    353036272022Monitoring KAT6A-CREBBP measurable residual disease in t(8;16) therapy-related acute myeloid leukemia.0
    356817322022Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia.0
    354228642022Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers.0
    346938562022MiR-143-3p Inhibits Cell Proliferation in Pedatric Acute Myeloid Leukemia via Inhibition of KAT6A.0
    354940432022Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer.0
    352266582022Expression of epigenetic pathway related genes in association with PD-L1, ER/PgR and MLH1 in endometrial carcinoma.0
    357660632022Second AML with disseminated intravascular coagulation and blast erythrophagocytosis revealing a t(8,16) KAT6A/CREBBP.0
    350758002022KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer.0
    347489932022Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature.0
    337702372022First case of pan-suture craniosynostosis due to de novo mosaic KAT6A mutation.0
    349302452021Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review.0
    346267702021The role of MOZ/KAT6A in hematological malignancies and advances in MOZ/KAT6A inhibitors.0
    344594522022miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression.0
    348424922021Copy number variations of the KAT6A gene are associated with body measurements of Chinese sheep breeds.0
    344395862021Sleep, Behavior, and Adaptive Function in KAT6A Syndrome.0
    343245032021Unravelling the genetic causes of multiple malformation syndromes: A whole exome sequencing study of the Cypriot population.0
    340391622021Ocular Findings in a Patient With KAT6A Mutation.0
    338133792021Therapy-related Myeloid Leukemia With the Translocation t(8;19)(p11;q13) Leading to a KAT6A-LEUTX Fusion Gene.0
    344972212021[Acute leukemia of infants and neonates].0
    328148472020Correction: KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.0
    325198302020Acute Monoblastic Leukemia with Erythrophagocytosis and Absence of KAT6A Rearrangement0
    333862512020Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A (KAT6A).0
    322129242020MOZ/KAT6A: a promising target for acute myeloid leukemia therapy.0
    328898042020Acute Myeloid Leukemia with t(8;16)(p11.2;p13.3)/ KAT6A-CREBBP in a Patient with an NF1 Germline Mutation and Clinical Presentation Mimicking Acute Promyelocytic Leukemia.0
    322425122020Targeting Histone Acetyltransferase MOZ/KAT6A as a New Avenue for Hematological Tumor Therapy.0
    319828752020Mosaic Small Supernumerary Marker Chromosome Derived from Five Discontinuous Regions of Chromosome 8 in a Patient with Neutropenia and Oral Aphthous Ulcer.0
    318072682019Highly aggressive undifferentiated small round blue cell tumor of foot with unique SMARCA1, KAT6A and NAV3 mutations.0

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    93765941997Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.Aguiar RC et al
    27907481989A complex t(3;8;17) involving breakpoint 8p11 in a case of M5 acute nonlymphocytic leukemia with erythrophagocytosis.Bertheas MF et al
    34761501987A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia.Heim S et al
    34726401987Three cases of translocation (8;16)(p11;p13) observed in acute myelomonocytic leukemia: a new specific subgroup?Laï JL et al
    111741182000[FGFR1 and MOZ, two key genes involved in malignant hemopathies linked to rearrangements within the chromosomal region 8p11-12].Pébusque MJ et al
    75961491995A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8:16)(p11:p13), in a patient with the variant t(8:19)(p11:q13)--case report and review of the literature.Stark B et al

    Summary

    Note

    Two distinct clinical syndromes have been associated with the 8p11-p12 region :
  • Stem-cell myeloproliferative disorder with FGFR1 rearrangement
  • AML M4 or M5 erythrophagocytosis-associated with MOZ rearrangement.
  • This t(8;19)(p11;q13) with MOZ involvement should not be confused with the t(8;19)(p11;q13) with FGFR1 involvement found in the stem-cell myeloproliferative disorder.

    The partners of 8p11 are 8q13, 14q11, 16p13, 19q13, 22q13 and 3q27, 17q12 in a complexe translocation t(3;8;17)(q27;p11;q12).

    • Citation

    Jacques Boyer

    t(8;19)(p11;q13) KAT6A/?

    Atlas Genet Cytogenet Oncol Haematol. 2003-12-01

    Online version: http://atlasgeneticsoncology.org/haematological/1315/img/js/lib/gene-fusions-explorer/