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+4 or trisomy 4

Written2000-07Alessandro Beghini
University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy

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ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
Atlas_Id 1011

Clinics and Pathology

Disease 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
  • the coincidence of +4 with t(8;21) or its variant t(6;21;8), observed in at least two cases of AML (M1 and M2), is therefore recurrent
  • 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

    Disease Acute lymphocytic leukaemia (ALL)
  • +4 has been described in two cases of T-cell acute lymphoblastic leukemia as the sole chromosomal anomaly
  • 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

    Disease Thecoma of the ovary
    Epidemiology +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.
    Prognosis no prognostic significance

    Disease +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


    Trisomy 4 leading to duplication of a mutated KIT allele in acute myeloid leukemia with mast cell involvement.
    Beghini A, Ripamonti CB, Castorina P, Pezzetti L, Doneda L, Cairoli R, Morra E, Larizza L
    Cancer genetics and cytogenetics. 2000 ; 119 (1) : 26-31.
    PMID 10812167
    Trisomy 4 in 'stem cell-like' leukemic cells of a patient with AML.
    Feuring-Buske M, Haase D, Könemann S, Troff C, Grove D, Hiddemann W, Wörmann B
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (8) : 1318-1320.
    PMID 7543964
    Trisomy 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, Shuster JJ, Carroll A, Look AT, Borowitz MJ, Crist WM, Nitschke R, Pullen J, Steuber CP, Land VJ
    Blood. 1992 ; 79 (12) : 3316-3324.
    PMID 1596572
    Trisomy 4 may occur in a broad range of hematologic malignancies.
    Kwong YL, Ha SY, Liu HW, Chan LC
    Cancer genetics and cytogenetics. 1993 ; 69 (2) : 139-140.
    PMID 8402553
    Trisomy 4 identifies a subset of acute nonlymphocytic leukemias.
    Mecucci C, Van Orshoven A, Tricot G, Michaux JL, Delannoy A, Van den Berghe H
    Blood. 1986 ; 67 (5) : 1328-1332.
    PMID 3697508
    Trisomy 12 and 4 in a thecoma of the ovary.
    Mrózek K, Limon J, Debniak J, Emerich J
    Gynecologic oncology. 1992 ; 45 (1) : 66-68.
    PMID 1318257
    MYC amplification in two further cases of acute myeloid leukemia with trisomy 4 and double minute chromosomes.
    O'Malley F, Rayeroux K, Cole-Sinclair M, Tong M, Campbell LJ
    Cancer genetics and cytogenetics. 1999 ; 109 (2) : 123-125.
    PMID 10087944


    This paper should be referenced as such :
    Beghini, A
    +4 or trisomy 4
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):129-130.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    External links

    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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