t(8;22)(p11;q13) KAT6A/EP300

2003-12-01   Jacques Boyer 

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology

Disease

Acute myelomonocytic or monocytic leukemia (M4, M5a, M5b) associated with erythrophagocytosis by blasts noted to various degree, one case is probably a therapy-related leukemia.

Epidemiology

Rare

Cytology

Erythrophagocytosis by blasts cells is occasionally found but not marked.

Prognosis

probably poor

Cytogenetics

Cytogenetics morphological

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

Additional anomalies

In one case association with trisomy 8

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 PHD-type zinc fingers.
MOZ is a histone acetyltransferase (HAT) and the fouding 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
EP300 (E1A binding protein p300)
Location
22q13.2
Note
Detection: FISH with the bacterial artificial chromosome clone H59D10
Protein description
Adenoviral E1A-associated protein p300 with acethyltransferase activity

Result of the Chromosomal Anomaly

Note

Gene fusion MOZ/P300

Description

MOZ is disrupted within the sequences encoding the acidic domain. Both fusion transcripts are expressed. The t(8;22) breakpoints occurs in MOZ codon 1117 within an exon of 4 kb.MOZ-p300 fusion is similar to MOZ-CBP described in the t(8;16) but involve p300 instead of CBP. The translocation creates in-frame fusion proteins (MOZ-p300 and p300-MOZ). The two fusion proteins retain the N-terminus portion of MOZ including the HAT domain.

Oncogenesis

How the MOZ-p300 fusion protein is involved in acute leukemia is not known, but it probably affects the chromatin condensation.

Bibliography

Pubmed IDLast YearTitleAuthors

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.
  • the t(8;22) (p11; q13) 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

    t(8;22)(p11;q13) KAT6A/EP300

    Atlas Genet Cytogenet Oncol Haematol. 2003-12-01

    Online version: http://atlasgeneticsoncology.org/haematological/1119/css/css/template-nav.css