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
    360776052022BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease.176
    334886792020Impaired Regulation of Histone Methylation and Acetylation Underlies Specific Neurodevelopmental Disorders.165
    367129632022The MOZ-BRPF1 acetyltransferase complex in epigenetic crosstalk linked to gene regulation, development, and human diseases.146
    334393822021Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.101
    348530792022KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.92
    378617172023KAT6A mutations in Arboleda-Tham syndrome drive epigenetic regulation of posterior HOXC cluster.83
    365372162023The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain.82
    384436622024A deep learning model of tumor cell architecture elucidates response and resistance to CDK4/6 inhibitors.80
    368682382023Dynamic chromatin accessibility tuning by the long noncoding RNA ELDR accelerates chondrocyte senescence and osteoarthritis.78
    400006512025KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan.76
    261242832015MicroRNA 665 Regulates Dentinogenesis through MicroRNA-Mediated Silencing and Epigenetic Mechanisms.76
    375776272023KAT6A mutations in Arboleda-Tham syndrome drive epigenetic regulation of posterior HOXC cluster.75
    241693042014Crosstalk between epigenetic readers regulates the MOZ/MORF HAT complexes.71
    372758502023The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver.70
    383182882023The value of genome-wide analysis in craniosynostosis.69
    343926142021KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer.68
    393800022024The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency.68
    379934742023Bioinformatics analysis and machine learning approach applied to the identification of novel key genes involved in non-alcoholic fatty liver disease.68
    395059712024ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.67
    365535672022Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome.66
    374639402023Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.66
    320107792020Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.60
    352479062022Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.57
    371277542023Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition.54
    339956582021KAT6A, a novel regulator of β-catenin, promotes tumorigenicity and chemoresistance in ovarian cancer by acetylating COP1.53
    389566952024Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.52
    359471262022MOZ is critical for the development of MOZ/MLL fusion-induced leukemia through regulation of Hoxa9/Meis1 expression.51
    383158492024A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism.51
    388314592024Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report.50
    385021382024High Clinical Exome Sequencing Diagnostic Rates and Novel Phenotypic Expansions for Nonisolated Microphthalmia, Anophthalmia, and Coloboma.50
    391290342024KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement.48
    389732552024KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer.46
    335414082021KAT6A regulates stemness of aging bone marrow-derived mesenchymal stem cells through Nrf2/ARE signaling pathway.44
    385187842024The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function.43
    356817322022Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia.43
    290211352017Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24 Binding.42
    233470992013The MYSTerious MOZ, a histone acetyltransferase with a key role in haematopoiesis.42
    319570182020Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort.41
    344594522022miR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression.41
    387587922024KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3.40
    252205922014KAT6A, a chromatin modifier from the 8p11-p12 amplicon is a candidate oncogene in luminal breast cancer.37
    302455132019KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.35
    388242442024Inhibition of lysine acetyltransferase KAT6 in ER(+)HER2(-) metastatic breast cancer: a phase 1 trial.34
    353322662022Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression.31
    349302452021Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review.31
    335526462021A Novel Frameshift Mutation in KAT6A Is Associated with Pancraniosynostosis.31
    344395862021Sleep, Behavior, and Adaptive Function in KAT6A Syndrome.29
    387410772024Neuropsychological profile associated with KAT6A syndrome: Emergent genotype-phenotype trends.21
    375051852023KAT6A::EP300 fusion in congenital myeloid sarcoma: Yet another novel molecular marker indicating spontaneous remission?: A case report.21
    365730382022The clinical spectrum of a nonsense mutation in KAT6A: a case report.20
    317544382017Three brothers with a nonsense mutation in KAT6A caused by parental germline mosaicism.20
    257287772015Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features.17
    375571812023Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.0
    298067012018Neonatal leukaemia.0
    300690492018Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.0
    382376012024Lysine acetyltransferase 6A maintains CD4(+) T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.0
    331305152020The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology.0
    383832162024Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy.0
    364009262023Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia.0
    397613812025Targeting KAT6A/B as a New Therapeutic Strategy for Cancer Therapy.0
    378630302023HATS off to KAT6A/B inhibitors: A new way to target estrogen-receptor-positive breast cancer.0
    346267702021The role of MOZ/KAT6A in hematological malignancies and advances in MOZ/KAT6A inhibitors.0
    320649382020Action plan for hit identification (APHID): KAT6A as a case study.0
    347489932022Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature.0
    322129242020MOZ/KAT6A: a promising target for acute myeloid leukemia therapy.0
    364561392022The Expression of Histone Acetyltransferase KAT6A in Non-small Cell Lung Cancer.0
    358922682022Speech and language development and genotype-phenotype correlation in 49 individuals with KAT6A syndrome.0
    322425122020Targeting Histone Acetyltransferase MOZ/KAT6A as a New Avenue for Hematological Tumor Therapy.0
    331441182021Targeting post-translational histone modifying enzymes in glioblastoma.0
    384462062024ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development.0
    348424922023Copy number variations of the KAT6A gene are associated with body measurements of Chinese sheep breeds.0
    372490022023DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A/KAT6B variants.0
    359764742022miR-339-3p inhibits cell growth and epithelial-mesenchymal transition in nasopharyngeal carcinoma by modulating the KAT6A/TRIM24 axis.0
    392353552024Circ_0005397 inhibits ferroptosis of pancreatic cancer cells by up-regulating PCBP2 through KAT6A/H3K9Ac.0
    259208102015MOZ and MORF acetyltransferases: Molecular interaction, animal development and human disease.0
    381828232024Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.0
    381430252024Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome.0
    348085022021KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP.0
    301441322018Histone Lysine and Genomic Targets of Histone Acetyltransferases in Mammals.0
    391531512024Expanding the Neuropsychological Phenotype of KAT6B Disorders: Overlapping Features with KAT6A Syndrome.0
    286362592017Variants in KAT6A and pituitary anomalies.0
    350758002022KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer.0
    344972212021[Acute leukemia of infants and neonates].0
    376518782023Discovery of N-(2-oxoethyl) sulfanilamide-derived inhibitors of KAT6A (MOZ) against leukemia by an isostere strategy.0
    312565872019Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A.0
    340391622021Ocular Findings in a Patient With KAT6A Mutation.0
    327798582020Rapidly progressing acute myeloid leukemia with KAT6A-LEUTX fusion in a newborn.0
    337395542021Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability.0
    399093742025Modulation of the Substrate Preference of a MYST Acetyltransferase by a Scaffold Protein.0
    328148472020Correction: KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.0
    384283782024The Mendelian disorders of chromatin machinery: Harnessing metabolic pathways and therapies for treatment.0
    395049392024Exploring Testicular Descent: Recent Findings and Future Prospects in Canine Cryptorchidism.0
    380299122024MYST family histone acetyltransferases regulate reproductive diapause initiation.0
    353036272022Monitoring KAT6A-CREBBP measurable residual disease in t(8;16) therapy-related acute myeloid leukemia.0
    307592702019Acute myeloid leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP in adults.0
    271333972016Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder.0
    397407282025Phenotypic variability in a family with an inherited KAT6A frameshift variant.0
    360532942022In Silico Positional Analogue Scanning with Amber GPU-TI.0
    276536922016Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity.0
    244460902014The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t(8;19)(p11;q13).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/t(8;19)(p11;q13)-kat6a