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

2011-02-01   Adriana Zamecnikova 

1.Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh, 70653 Kuwait
2.Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark

Clinics and Pathology


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).


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 stem cell origin

Suggested involvement of a pluripotent stem cell or a myeloid progenitor cell; very rarely in lymphoid lineage.


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).


6 cases to date, children aged 6 months to 5 years, male predominance; sex ratio 4M/2F.


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).


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.

Genes Involved and Proteins

Gene name
FOXO4 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7)
Dna rna description
AFX consists of two exons and encodes for a protein of 501 amino acids.
Protein description
Transcription factor; high degree of homology between AFXI and the forkhead protein family and highly homologous to the human FKHR protein.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Dna rna description
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 description
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


5 MLL - AFX 3 as well as the 5 AFX - MLL 3.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).


Pubmed IDLast YearTitleAuthors
77801451995Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses.Bentz M et al
90102211997Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23).Borkhardt A et al
95932861998Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.Harrison CJ et al
155436022005Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes.Kalla C et al
69622011982Acute myelogenous leukemia in a child with primary involvement of chromosomes 11 and X.Nacheva E et al
75295521994Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.Parry P et al
27874771989Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia.Pui CH et al
29521821987An analysis of leukemic cell chromosomal features in infants.Pui CH et al
27583951989Cytogenetics of childhood acute nonlymphocytic leukemia.Raimondi SC et al
41186521973Characterisation of malignant mediastinal lymphoid neoplasm (Sternberg sarcoma) as thymic in origin.Smith JL et al


Fusion gene

KMT2A/FOXO4 KMT2A (11q23.3) FOXO4 (Xq13.1) COF 1976
Atlas Image
t(X;11)(q13;q23) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.


Adriana Zamecnikova

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

Atlas Genet Cytogenet Oncol Haematol. 2011-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1127/t(x;11)(q13;q23)

Historical Card

2001-08-01 t(X;11)(q13;q23) KMT2A/FOXO4 by  Stig E Bojesen 

Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev DK-2730, Denmark

External Links