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12p abnormalities in myeloid malignancies

Written1998-05Chrystele Bilhou-Nabera
Cytogénétique,Laboratoire d'Hématologie-Pr RAPHAEL, Pav BROCA - 4me étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France

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ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1032
  del(12p)  Partial karyotypes with 12p deletions (A); G- banding: seven left – Courtesy Adriana Zamecnikova; following two - Courtesy Jean-Luc Lai and Alain Vanderhaegen; following: R- banding - Courtesy Jean-Luc Lai and (following ) Jean Loup Huret. Hybridization with LSI ETV6 break apart probe (Abbott molecular, US) showing deletion of the gene in metaphase and interphase cells (B,C). Partial ETV6 deletion as a result of del(12)(p13). – Courtesy Adriana Zamecnikova.

Clinics and Pathology

Epidemiology 12p abnormalities are common in a broad spectrum of haematological malignancies (acute lymphoblastic (ALL) or acute myeloid (AML) leukaemias, myelodysplastic (MDS) or chronic myeloproliferative syndromes, non-Hodgkin's lymphomas; observed in about 5% of acute myeloid leukaemias and myelodysplastic syndromes; characteristic of secondary leukaemia after prior mutagenic exposure (10%) and associated with a poor prognosis (karyotypes mostly complex)


Cytogenetics Morphological
  • sole anomaly in 20 %; numerical and structural rearrangements of chromosomes 5 and 7 frequently associated (found in 50% in de novo cases).
  • del(12p): due to the very heterogeneous breakpoints in 12p (assigned to all chromosome bands), no cytogenetic subgroups are defined; deletion in 12p is generally associated with a poor prognosis; however, different clinical courses are defined concerning the magnitude of 12p; a group with small deletions has a better prognosis than patients with 12p abnormalities in general and a lower tendency to additional chromosomal rearrangements; submicroscopic deletions of 12p are much more common in lymphoid than in myeloid malignancies; a minimal interstitial deletion region is described, involving ETV6 and CDKN1B genes; homozygous deletion of CDKN1B is rare (the other wild allele never found mutated); none of the malignancies with disease specific changes displayed submicroscopic 12p deletions.
  • dup(12)(p11.2p13) described in one MDS case after benzole agent exposure
  • additions are frequent, considered as imbalanced translocations
  • translocations: translocations or dicentrics involving 12p are mostly associated with loss of 12p material; a lot of partner bands are described; chromosome 12 breakpoint is most often localized in 12p13, involving ETV6 gene, with fusion of 5' end of ETV6 with 3' end of the partner, and sometimes accompanied with a concomitant deletion of the other ETV6 allele:
  • t(3;12)(q23;p12.3): described as reciprocal and recurrent, involving ETV6 (heterogeneous breakpoints described) and EVI1, and associated with a poor prognosis.
  • t(4;12)q11q13;p12;p13): associated with specific clinical features: CD7-positive AML, three-lineage dysplasia, blood and bone marrow basophilia
  • t(5;12)(q33;p13): recurrent, described in chronic myelomonocytic leukemia: fusion between HLH domain of ETV6 and transmembrane and cytoplasmic kinase domains of PDGFRb; a variant t(10;12)(q24;p13) is described in MDS in progression with eosinopilia and monocytosis.
  • t/dic(12;13): representing up to 20% of 12p rearrangements in one study, associated with a poor prognosis
  • t(12;22)(p13;q11): resulting in MN1-ETV6 fusion gene (where breakpoint, 5' of, or in, ETV6 HLH domain, is the sole exception), and reported in myeloid malignancies (AML and MDS)
  • other translocations involving ETV6: t(5;12)(q31;p12) in "atypical CML", t(6;12)(p21;p13) in MDS, t(7;12)(p15;p13), t(7;12)(q36;p13) in AML, t(9;12;14)(q34;p13;q22) in AML, ... and the never-up-to-date following list: t(6;12)(q23;p13), t(12;17)(p11.2;q11), t/dic(12;20)(p12-p13;p11.2-q13), i(12p) where implication of ETV6 gene is not yet proven.
  • Bibliography

    Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.
    Andreasson P, Johansson B, Billström R, Garwicz S, Mitelman F, Höglund M
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (3) : 390-400.
    PMID 9529134
    Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11.
    Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, Riegman P, Lekanne Deprez R, Zwarthoff E, Hagemeijer A
    Oncogene. 1995 ; 10 (8) : 1511-1519.
    PMID 7731705
    Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.
    Golub TR, Barker GF, Lovett M, Gilliland DG
    Cell. 1994 ; 77 (2) : 307-316.
    PMID 8168137
    Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.
    Raynaud SD, Baens M, Grosgeorge J, Rodgers K, Reid CD, Dainton M, Dyer M, Fuzibet JG, Gratecos N, Taillan B, Ayraud N, Marynen P
    Blood. 1996 ; 88 (2) : 682-689.
    PMID 8695816
    TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies.
    Sato Y, Suto Y, Pietenpol J, Golub TR, Gilliland DG, Davis EM, Le Beau MM, Roberts JM, Vogelstein B, Rowley JD
    Blood. 1995 ; 86 (4) : 1525-1533.
    PMID 7632960
    Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with AML or MDS and abnormalities of the short arm of chromosome 12.
    Streubel B, Sauerland C, Heil G, Freund M, Bartels H, Lengfelder E, Wandt H, Ludwig WD, Nowotny H, Baldus M, Grothaus-Pinke B, Büchner T, Fonatsch C
    British journal of haematology. 1998 ; 100 (3) : 521-533.
    PMID 9504635
    Fluorescence in situ hybridization characterization of new translocations involving TEL (ETV6) in a wide spectrum of hematologic malignancies.
    Wlodarska I, La Starza R, Baens M, Dierlamm J, Uyttebroeck A, Selleslag D, Francine A, Mecucci C, Hagemeijer A, Van den Berghe H, Marynen P
    Blood. 1998 ; 91 (4) : 1399-1406.
    PMID 9454771


    This paper should be referenced as such :
    Bilhou-Nabera, C
    12p abnormalities in myeloid malignancies
    Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):125-126.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes MNX1

    External links

    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]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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