+4 or trisomy 4

2000-07-01   Alessandro Beghini 

1.University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy

Clinics and Pathology


Acute myeloid leukaemia (AML)


  • +4 as the sole anomaly is a rare chromosomal abnormality associated with a specific subtype of primary AML and secondary (treatment related) AML with myelomonocytic morphology; it has been found with the same frequence in the M1-M2 and M4 French-American-British (FAB) phenotypes
  • association of +4 with double minute chromosomes has been described in ten cases; five with AML-M2, two with AML-M4, one with refractory anemia with excess of blasts in transformation (RAEB-T), one with chronic myelomonocytic leukemia (CMMoL) and one with unclassified preleukemia
  • +4 has been described in two cases of T-cell acute lymphoblastic leukemia as the sole chromosomal anomaly
  • Prognosis

    apparently +4 has no prognostic significance in AML; with the exception of the cases bearing c-Kit mutations who are associated with a rapid disease progression


    Acute lymphocytic leukaemia (ALL)


  • combined trisomies of chromosomes 4 and 10 are found in children with B-progenitor cell acute lymphoblastic leukemia with a favourable prognostic association
  • Prognosis

    patients with chromosomes 4 and 10 trisomies have an extremely favourable 4-year event-free survival (EFS) after antimetabolite-based chemoterapy


    Thecoma of the ovary


    +4 associated with +12 has been described in two cases of fibrothecoma and in one case of thecoma; it has been suggested that acquisition of trisomy 4 may constitute a second cytogenetic step in tumor progression of ovarian thecoma/fibrothecoma.


    no prognostic significance


    +4 has been found as the sole aberration only in one case of uterine leiomyoma


    trisomy 4 was proven to lead to duplication of Asp816Tyr mutation of c-Kit gene (that maps to 4q12 ) in a case of M2-AML with mast cell involvement


    Pubmed IDLast YearTitleAuthors
    108121672000Trisomy 4 leading to duplication of a mutated KIT allele in acute myeloid leukemia with mast cell involvement.Beghini A et al
    75439641995Trisomy 4 in 'stem cell-like' leukemic cells of a patient with AML.Feuring-Buske M et al
    15965721992Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B-progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group study.Harris MB et al
    84025531993Trisomy 4 may occur in a broad range of hematologic malignancies.Kwong YL et al
    36975081986Trisomy 4 identifies a subset of acute nonlymphocytic leukemias.Mecucci C et al
    13182571992Trisomy 12 and 4 in a thecoma of the ovary.Mrózek K et al
    100879441999MYC amplification in two further cases of acute myeloid leukemia with trisomy 4 and double minute chromosomes.O'Malley F et al


    Alessandro Beghini

    +4 or trisomy 4

    Atlas Genet Cytogenet Oncol Haematol. 2000-07-01

    Online version: http://atlasgeneticsoncology.org/haematological/1011/+4-or-trisomy-4