Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

t(X;11)(q13;q23) KMT2A::FOXO4

Written2011-02Adriana Zamecnikova
Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh, 70653 Kuwait
This article is an update of :
2001-08Stig E Bojesen
Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark

(Note : for Links provided by Atlas : click)


ICD-Morpho 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged
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
Atlas_Id 1127
  t(X;11)(q13;q23) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.

Clinics and Pathology

Disease Described in infants and young children; 4 cases of acute myeloid leukemia (AML) (Pui et al., 1987; Raimondi et al., 1989; Pui et al., 1989; Harrison et al., 1998) and one case of acute lymphoblastic leukemia (ALL) (Smith et al., 1973). With one exception, the FAB types in cases of AML were M4. Peripheral leucocytes at diagnosis of this ALL case were cultured and are presently known as the KARPAS-45 cell line (Karpas et al., 1977). In addition, MLL/AFX1 fusion was confirmed in an AML case with highly complex change originally published involving the Xq22 locus (Nacheva et al., 1982; Parry et al., 1994; Borkhardtet al., 1997).
Note This translocation has also been found in 2 cases of CLL (Bentz et al., 1995; Kalla et al., 2005). In one case a t(X;11)(q13;q23) was cloned revealing the involvement of BRWD3 gene recently located on Xq21.1 (Kalla et al., 2005).
Phenotype / cell stem origin Suggested involvement of a pluripotent stem cell or a myeloid progenitor cell; very rarely in lymphoid lineage.
Etiology No known prior exposure; case of AML M2 developed in a 6 years old male previously treated by chemotherapy and radiotherapy for acute lymphoblastic leukemia (Harrison et al., 1998).
Epidemiology 6 cases to date, children aged 6 months to 5 years, male predominance; sex ratio 4M/2F.
Clinics From the known data: WBC: 21.6 to 91x109/L, case with a complex t(X;11) associated with fever, enlargement of the liver, spleen and parotid glands, blood in the stool (Karpas et al., 1977); mediastinal mass, dyspnoea, no hepatosplenomegaly, WBC: 5x109/L in T-ALL (Smith et al., 1973).
Prognosis Survival: poor prognosis; 3 patients died within a year after diagnosis, and one patient died after 24.5 months.


Breakpoints difficult to ascertain in suboptimal preparations.


Additional anomalies Part of a highly complex change in one case; in KARPAS 45: Hypotetraploidy. -Y, -3, +6, -14, -18 t(1;5)(q21;q12.2)x2, del4(4)(q22), del(16)(q22).

Genes involved and Proteins

Note Cloning and characterization of AFX the gene that fuses to MLL in one case of AML and in the leukemic cell line.
Gene NameFOXO4 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7)
Location Xq13.1
Dna / Rna AFX consists of two exons and encodes for a protein of 501 amino acids.
Protein Transcription factor; high degree of homology between AFXI and the forkhead protein family and highly homologous to the human FKHR protein.
Gene NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Dna / Rna The Mixed-Lineage Leukemia gene consists of at least 36 exons, encoding a 3969 amino-acid nuclear protein with a molecular weight of nearly 430 kDa.
Protein Multidomain molecule; shares homology with the Drosophila trithorax protein; function as a positive regulator of gene expression in embryonic development and hematopoiesis.

Result of the chromosomal anomaly

Hybrid gene
Note 5' MLL - AFX 3' as well as the 5' AFX - MLL 3'.
Fusion Protein
Note Chimeric proteins that contain the N-terminus of MLL; hybrid transcript MLL-AFX1 contains the code for the following domains: AT-hook + DNA methyltransferase (from MLL) + part, aa 147-187 of the DNA-binding domain (from AFX1).

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses.
Bentz M, Huck K, du Manoir S, Joos S, Werner CA, Fischer K, Dohner H, Lichter P.
Blood. 1995 Jun 15;85(12):3610-8.
PMID 7780145
Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).
Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J, Hammermann J, Henn T, Lampert F.
Oncogene. 1997 Jan 16;14(2):195-202.
PMID 9010221
Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.
Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff M, Mugneret F, Moorman AV, Secker-Walker LM.
Leukemia. 1998 May;12(5):811-22.
PMID 9593286
Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes.
Kalla C, Nentwich H, Schlotter M, Mertens D, Wildenberger K, Dohner H, Stilgenbauer S, Lichter P.
Genes Chromosomes Cancer. 2005 Feb;42(2):128-43.
PMID 15543602
The Establishment and Cytological, Cytochemical and Immunological Characterisation of Human Haemic Cell Lines: Evidence for Heterogeneity.
Karpas A, Hayhoe FGJ, Greenberger JS, Barker CR, Cawley JC, Lowenthal RM, Moloney WC.
Leukaemia Res 1977; 1 : 35-49.
Acute myelogenous leukemia in a child with primary involvement of chromosomes 11 and X.
Nacheva E, Fischer P, Haas O, Manolova Y, Manolov G, Levan A.
Hereditas. 1982;97(2):273-88.
PMID 6962201
Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.
Parry P, Wei Y, Evans G.
Genes Chromosomes Cancer. 1994 Oct;11(2):79-84.
PMID 7529552
Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia.
Pui CH, Behm FG, Raimondi SC, Dodge RK, George SL, Rivera GK, Mirro J Jr, Kalwinsky DK, Dahl GV, Murphy SB.
N Engl J Med. 1989 Jul 20;321(3):136-42.
PMID 2787477
An analysis of leukemic cell chromosomal features in infants.
Pui CH, Raimondi SC, Murphy SB, Ribeiro RC, Kalwinsky DK, Dahl GV, Crist WM, Williams DL.
Blood. 1987 May;69(5):1289-93.
PMID 2952182
Cytogenetics of childhood acute nonlymphocytic leukemia.
Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL.
Cancer Genet Cytogenet. 1989 Jul 1;40(1):13-27.
PMID 2758395
Characterisation of malignant mediastinal lymphoid neoplasm (Sternberg sarcoma) as thymic in origin.
Smith JL, Clein GP, Barker CR, Collins RD.
Lancet. 1973 Jan 13;1(7794):74-7.
PMID 4118652


This paper should be referenced as such :
Zamecnikova, A
Atlas Genet Cytogenet Oncol Haematol. 2011;15(9):761-762.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Bojesen, SE. t(X;11)(q13;q23). Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):290-291.

Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(X;11)(q13;q23) KMT2A/FOXO4

External links

KMT2A (11q23.3) FOXO4 (Xq13.1)

Mitelman databaset(X;11)(q13;q23)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9807/3) -   [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 ( 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]
COSMIC_fusionKMT2A/FOXO4 KMT2A (11q23.3) FOXO4 (Xq13.1)   [fusion1976]  
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 16:37:06 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us