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t(4;11)(q21;q23) KMT2A/AFF1

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


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 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 1051
  t(4;11)(q21;q23) ) G-banding (left) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap,>; R- banding (right) - Jean Loup Huret (top), - Courtesy Christiane Charrin (middle), - Courtesy Hossein Mossafa (bottom and FISH).

Clinics and Pathology

Disease ALL mainly
Phenotype / cell stem origin B-ALL (L1 or L2), biphenotypic AL, at times AML (M4/M5 types maily); has been found in treatment related leukaemia; T-ALL as an exception
Epidemiology children (including infants: named a congenital leukaemia when before 1 yr or 2 yrs of age) and adults; half cases are under 4 yrs, 1/3 under 1yr; unbalanced sex ratio in cases < 4 yrs (1M/2F); 2 to 5% of ALL
Clinics organomegaly, CNS involvement not rare; can be secondary to epipodophyllotoxins (antitopoisomerase drugs for various cancers treatment); high WBC (median around 200 X 109/l), anaemia, thrombocytopenia; 90% blasts in blood
Cytology typically CD19+; may be accompanied with myeloid markers
Treatment bone marrow transplantation is highly indicated, as the prognosis is very poor
Prognosis CR is obtained but is promptly followed by relape; median survival: 7 mths in adult cases, 9 mths in children


  i(7q) R- banding - Jean-Loup Huret (left), - Courtesy Christiane Charrin (right).
Additional anomalies in 1/4 of cases at diagnosis, clonal evolution to hyperploidy: i(7q) in 10%, +X, + Mar, +6, +8, +19, +21, +13, +10, +14; no difference in outcome
Variants three way complex t(4;11;Var) exist and showed that the crucial event lies on der(11)

Genes involved and Proteins

Gene Name AFF1
Location 4q21
Dna / Rna 10.5-12 kb mRNA
Protein contains a nuclear targeting sequence; nuclear localisation; function: transcription activator
Gene Name KMT2A
Location 11q23
Dna / Rna 21 exons, spanning over 100 kb; 13-15 kb mRNA
Protein 431 kDa; 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' MLL-3' AF4; variable breakpoints
Transcript 12kb
Fusion Protein
Description e.g. 2319 amino acids; 240 kDa; N-term AT hook and DNA methyltransferase from MLL fused to AF4 C-term; the reciprocal ( AF4-MLL) may or may not be expressed; quite similar to the MLL/ENL fusion protein found with t(11;19)
Expression Localisation nuclear localisation

To be noted

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


Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group.
Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, Steinherz PG, Zeltzer P, Hammond D, Reaman GH
Blood. 1994 ; 83 (8) : 2274-2284.
PMID 8161794
Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases.
Lampert F, Harbott J, Ludwig WD, Bartram CR, Ritter J, Gerein V, Neidhardt M, Mertens R, Graf N, Riehm H
Blut. 1987 ; 54 (6) : 325-335.
PMID 3496135
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases.
Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP
Blood. 1991 ; 77 (3) : 440-447.
PMID 1991161
Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations.
Schoch C, Rieder H, Freund M, Hoelzer D, Riehm H, Fonatsch C
Annals of hematology. 1995 ; 70 (4) : 195-201.
PMID 7748964


This paper should be referenced as such :
Huret, JL
Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):96-97.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 5 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(4;11)(q21;q23) KMT2A/AFF1

External links

KMT2A (11q23.3) AFF1 (4q21.3)

KMT2A (11q23.3) AFF1 (4q21.3)

Mitelman databaset(4;11)(q21;q23) [Case List]    t(4;11)(q21;q23) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9807/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9813/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionKMT2A/AFF1 KMT2A (11q23.3) AFF1 (4q21.3)   [fusion1799]   [fusion1800]   [fusion1801]   [fusion1802]   [fusion1827]   [fusion1828]   [fusion1829]   [fusion1830]   [fusion1947]   [fusion1948]   [fusion1949]   [fusion1951]   [fusion1953]   [fusion1954]   [fusion1955]   [fusion1956]   [fusion1957]   [fusion1958]   [fusion2023]   [fusion2024]   [fusion2066]   [fusion2067]   [fusion2068]   [fusion2073]   [fusion2074]   [fusion2090]   [fusion2091]   [fusion2092]  
TICdbKMT2A/AFF1  KMT2A (11q23.3) AFF1 (4q21.3)
Disease databaset(4;11)(q21;q23) KMT2A/AFF1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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indexed on : Tue Mar 14 13:54:44 CET 2017

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