inv(8)(p11q13) KAT6A/NCOA2

2003-12-01   Jacques Boyer 

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology


  • Acute myelomonocytic or monocytic leukaemia (M4, M5a, M5b FAB) with erythrophagocytosis by blasts.
  • Acute myeloblastic leukemia M0/M1 FAB (one case).
  • Epidemiology

    Rare. Young age (6 patients, median : 23.5 years) and female sexe.


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


    Probably poor.


    Cytogenetics morphological

    Inv(8) (p11q13) is a variant of t(8;16) (p11;p13)

    Additional anomalies

    In one case der(10)t(1;10)(q25;p15)

    Genes Involved and Proteins

    Gene name
    KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3
    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
    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
    NCOA2 (nuclear receptor coactivator 2)
    Aliases : GRIP1, NCoA-2.
    Nuclear receptors are ligand-inductible transcription factors with three structural domains : an activation function AF-1, a DNA-binding domain and a second activation function AF-2 that is mediated by nuclear coactivators (NRCoAs) : TIF2 was recently shown to be one such mediators of AF-2 function.
    Detection by FISH : PAC clone 192D10
    Protein description
    The TIF-2 protein is homologous to other NRCoAs specically SRC-1 (alias NcoA-1). This protein have HAT activity and also interacts directly with CBP. It is likely that TIF-2 mediates transcriptional activation by a mechanism involving chromatin remodeling.

    Result of the Chromosomal Anomaly


    The fusion gene produces a mRNA containing the 5¹ end of MOZ appended in translational frame to the 3¹ end of TIF2.
    The inv(8) MOZ breakpoint is distinct from the breakpoint in the MOZ -CBP fusion.
    The fusion product retains the zinc fingers, the HAT domain of MOZ along with the HAT domains and CBP interacting domain of TIF2.MOZ-TIF2


    The ability of HATs to affect the chromatin structure and regulate gene expression is well appreciated. How the MOZ-TIF2 fusion protein is involved in acute leukemia is not known, but it probably affects the chromatin condensation. It may modulate or augment the transcriptional activity of genes normaly regulated by MOZ or it may serve as a bridge between MOZ and CBP.
    Recently, it was demonstrated that MOZ-TIF2 has transforming properties in vitro and causes AML. The C2HC nucleosome recognition motif of MOZ and MOZ-TIF2 interaction with CBP are essential for transformation.


    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
    95583661998A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.Carapeti M et al
    126765842003MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP.Deguchi K 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


    Fusion gene

    KAT6A/NCOA2 KAT6A (8p11.21) NCOA2 (8q13.3) M inv(8)(p11q13)|KAT6A/NCOA2 KAT6A (8p11.21) NCOA2 (8q13.3) TIC


    Two distinct clinical syndromes have been associated with the 8p11-12 region :
  • Stem-cell myeloproliferative disorder with FGFR1 rearrangement
  • AML M4 or M5 erythrophagocytosis-associated with MOZ rearrangement.
  • the inv(8)(p11q13) involves MOZ

    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

    inv(8)(p11q13) KAT6A/NCOA2

    Atlas Genet Cytogenet Oncol Haematol. 2003-12-01

    Online version: