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t(11;16)(q23;p13.3) KMT2A/CREBBP

Written2009-03Elise Labis
Laboratory of Medical Genetics, Hospital Jeanne de Flandre, University Hospital Regional Center-CHRU, Avenue Eugène Avinée, 59037 Lille cedex, France

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ICD-Morpho 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged
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 1120
  t(11;16)(q23;p13.3) G-banding.

Clinics and Pathology

Disease Treatment-related myelodysplastic syndrome (t-MDS) or treatment-related acute leukaemia, usually myeloblastic (t-AML), less often lymphoblastic (t-ALL).
Two case reports describe a de novo leukaemia with t(11;16)(q23;p13.3): an AML-M4 (Glassman et al., 2003) and an infant ALL, which switch into AML with retention of the translocation (Stasik et al., 2006).
Phenotype / cell stem origin Variable phenotypes: most often LAM4 in t-AML (but also LAM5a and LAM2); chronic myelomonocytic leukaemia (CMMoL) in t-MDS.
Etiology Chemotherapy for other primary malignancies (including leukaemia, lymphoma and solid tumors) using topoisomerase II inhibitors (epipodophyllotoxins or anthracyclins).
Epidemiology Rare translocation (about twenty cases described), found at any age, from infancy to elder age.
Prognosis Poor, as in other therapy-related leukaemia.


Cytogenetics Morphological Can be seen with G-banding: chromosome 11 appears shortened, chromosome 16 enlarged (11q- and 16p+).
Cytogenetics Molecular FISH may be needed.
  Fish studies using a commercially available MLL break-apart probe (Vysis® LSI® MLL Dual Color). The derivative 11 shows a single green signal indicating rearrangement of the MLL locus. The derivative 16 has the translocated portion of the MLL indicated by a single red signal.
Additional anomalies In half cases about, no recurrent additional cytogenetic anomalies.

Genes involved and Proteins

Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Dna / Rna 37 exons, spanning over 100 kb.
Protein MLL is a "multipartner" gene involved in multiple rearrangements: the most frequent partners are AF4 in 4q21, AF6 in 6q27, AF9 in 9p22, ELL in 19p13.1 and ENL in 19p13.3.
MLL is a major regulator of hematopoesis and embryonic development, through HOX genes expression regulation. MLL binds to promotors of HOX genes such as Hoxa7 and Hoxa9 (proteins which regulate hematopoiesis and are normally expressed only in early hematopoietic progenitors) through acetylation and methylation of histones.
Gene NameCREBBP (CREB binding protein)
Location 16p13.3
Dna / Rna About 154 kb, 32 exons.
Protein It is a transcriptional coactivator involved in coordonating signal from many sequence-specific activators to modulate transcription and/or cell cycle progression. It has endogenous histone acetyltransferase activity and may contribute to transcriptional regulation via targeted acetylation of chromatin.

Result of the chromosomal anomaly

Hybrid gene
Transcript 5' MLL - 3' CBP on the der(11) and 5' CBP - 3' MLL on the der(16).
Variable breakpoints: In MLL, almost all of the breakpoints occurs in an 8.3-kb fragment known as the breakpoint cluster region (BCR), encompassing exons 8-14. In CBP, the genomic breakpoints clustered in an 8.2-kb region of intron 3 (BCR 8.2kb), which is different of the breakpoints in CBP for patients with t(8;16) clustered in a 2.3-kb region in intron 2 (BCR 2.3kb).
Fusion Protein
Description N-Term from MLL (containing the AT-hooks and repression domain) fused to the C-Term of CBP (almost always including the CREB binding domain, bromodomain, histone acetyltransferase domain).


Translocation (11;16)(q23;p13) acute myelogenous leukemia and myelodysplastic syndrome.
Glassman AB, Hayes KJ.
Ann Clin Lab Sci. 2003 Summer;33(3):285-8.
PMID 12956443
All patients with the t(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders.
Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelberger B, Behm F, Doggett NA, Borrow J, Zeleznik-Le N.
Blood. 1997 Jul 15;90(2):535-41.
PMID 9226152
Infant acute lymphoblastic leukemia with t(11;16)(q23;p13.3) and lineage switch into acute monoblastic leukemia.
Stasik C, Ganguly S, Cunningham MT, Hagemeister S, Persons DL.
Cancer Genet Cytogenet. 2006 Jul 15;168(2):146-9.
PMID 16843104
Characterization of genomic breakpoints in MLL and CBP in leukemia patients with t(11;16).
Zhang Y, Zeleznik-Le N, Emmanuel N, Jayathilaka N, Chen J, Strissel P, Strick R, Li L, Neilly MB, Taki T, Hayashi Y, Kaneko Y, Schlegelberger B, Rowley JD.
Genes Chromosomes Cancer. 2004 Nov;41(3):257-65.
PMID 15334549


This paper should be referenced as such :
Huret, JL
Atlas Genet Cytogenet Oncol Haematol. 1998;2(2):60-61.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(11;16)(q23;p13.3) KMT2A/CREBBP

External links

KMT2A (11q23.3) CREBBP (16p13.3)

KMT2A (11q23.3) CREBBP (16p13.3)

Mitelman databaset(11;16)(q23;p13.3)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9807/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9813/3) -   [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]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionKMT2A/CREBBP KMT2A (11q23.3) CREBBP (16p13.3)   [fusion1874]   [fusion1875]   [fusion1876]   [fusion2093]   [fusion2095]   [fusion2097]   [fusion2098]   [fusion2109]   [fusion2110]   [fusion2116]   [fusion2117]  
TICdbKMT2A/CREBBP  KMT2A (11q23.3) CREBBP (16p13.3)
REVIEW articlesautomatic search in PubMed
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