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t(9;11)(p21;q23) KMT2A::MLLT3

Written2016-03Jeroen Knijnenburg, H. Berna Beverloo
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
This article is an update of :
1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Abstract Review on t(9;11)(p21;q23), with data on clinics, and the genes involved.

Keywords chromosome 9; chromosome 11; acute myeloid leukemia; KMT2A; MLLT3.

(Note : for Links provided by Atlas : click)


ICD-Morpho 9897/3 AML with t(9;11)(p22;q23); MLLT3-MLL
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
Atlas_Id 1001
  t(9;11)(p21;q23) KMT2A/MLLT3 G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top 2 rows), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (rows 3 to 6); Courtesy  Adriana Zamecnikova (rows 7 and 8); R-banding (right): top: - Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski, center top: t(9;11)+der(9)t(9;11) - Courtesy Christiane Charrin; bottom 2: - Courtesy Hossein Mossafa. FISH: “Red” chromosomes - Courtesy Pascale Cornillet-Lefebvre and Stéphanie Struski. The probe is MLL; one signal is on the normal 11, one signal on the der(11), and one signal (arrow) on the der(9); pale blue chromosomes - Courtesy Hossein Mossafa (AN: abnormal). (); bottom 3: Hybridization with Kreatech KMT2A/MLLT3 t(9;11) fusion probe (Leica Biosystems, US) showing hybridization on normal (A) and on metaphases with t(9;11) (B,C). - Courtesy  Adriana Zamecnikova.

Clinics and Pathology

Disease Acute myeloid leukemia (AML).
Phenotype / cell stem origin Most often found in acute monocytic and myelomonocytic leukaemias, although occasionally also seen in AML with or without maturation (WHO 2008).
M5 most often (especially M5a, M4); both found in de novo and therapy related AML with antitopoisomerase II drugs (epipodophyllotoxins, anthracyclins, actinomycin D).
Immunophenotype typically shows positivity for CD11, CD13, CD15 and CD33, but less often shows positivity for CD14, CD34 and lymphoid markers.
Epidemiology May occur at any age, but is more common in children, being present in 5-12% of paediatric and 1-2% of adult AML, and equally common in males and females.
Clinics Organomegaly, frequent central nervous system (CNS) involvement, especially in de novo cases; no preceding myelodysplastic phase, unlike classic therapy related AML with chromosome 5 and/or 7 involvement, short interval from initial drug therapy (may even be of 1-2 yrs). Patients may present with disseminated intravascular coagulation and may have tissue infiltration.
Cytology Absence of trilineage dysplasia, unlike classic therapy related AML.
Prognosis Survival is described as poor to intermediate, being superior to AML with other KMT2A translocations.


Cytogenetics Morphological May easily be overlooked. Previously described as t(9;11)(p22;q23) based on band estimation, but nowadays it is known that MLLT3 is located in 9p21.3 based on molecular positioning.
Cytogenetics Molecular FISH or RT-PCR is indicated in cases with poor chromosome morphology or in cases where the translocation is expected in cases based on morphology, immunophenotype or clinical presentation.
Additional anomalies None in 70% of cases, +8 in 20%, less frequently: additional trisomies of chromosome 6, 19 or 21.
Variants Complex 3 way translocations t(9;11;Var) involving a (variable) third chromosome and insertions have been described, and showed that der(11) is the crucial on

Genes involved and Proteins

Gene NameMLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3)
Location 9p21.3
Protein Contains a nuclear targeting sequence; transcriptional activator; nuclear localisation.
Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Protein Contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation.

Result of the chromosomal anomaly

Hybrid gene
Description 5' KMT2A- 3' MLLT3; variable breakpoints.
Fusion Protein
Description N-term -- AT hook and DNA methyltransferase from KMT2A (1444 amino acids) fused to the 192 C-term amino acids from MLLT3 (as breakpoints are variable, this is only an exemple); 180 kDa.
Expression Localisation Nuclear localisation.

To be noted

You may also have a glance at 11q23 rearrangements, which gives an overview of related diseases.


Implication of prior treatment with drug combinations including inhibitors of topoisomerase II in therapy-related monocytic leukemia with a 9;11 translocation.
Albain KS, Le Beau MM, Ullirsch R, Schumacher H
Genes, chromosomes & cancer. 1990 ; 2 (1) : 53-58.
PMID 2177642
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.
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Blood 2009 ; 114(12):2489-2496.
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Blood. 2010 Jan 21;115(3):453-74.
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Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.
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Oncogene. 1996 ; 13 (9) : 1945-1953.
PMID 8934541
Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia.
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This paper should be referenced as such :
Jeroen Knijnenburg, H Berna Beverloo
t(9;11)(p21;q23) KMT2A/MLLT3
Atlas Genet Cytogenet Oncol Haematol. 2016;20(12):613-615.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. t(9;22)(q34;q11) in CML. Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):98-100.

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


Translocations implicated (Data extracted from papers in the Atlas)

 t(9;11)(p22;q23) KMT2A/MLLT3

External links

KMT2A (11q23.3) MLLT3 (9p21.3)

Mitelman databaset(9;11)(p22;q23)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9897/3) -   [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]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
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