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Leukaemia Section
Mini Review
t(X;11)(q13;q23)
Adriana Zamecnikova
Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh,
70653 Kuwait (AZ)
Published in Atlas Database: February 2011
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0X11ID1127.html
DOI: 10.4267/2042/46030
This article is an update of : Bojesen SE. t(X;11)(q13;q23). Atlas Genet Cytogenet Oncol Haematol 2001;5(4):291-292.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology
a t(X;11)(q13;q23) was cloned revealing the
involvement of BRWD3 gene recently located on
Xq21.1 (Kalla et al., 2005).
Identity
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).
t(X;11)(q13;q23) G- banding - Courtesy Melanie Zenger and
Claudia Haferlach.
Clinics and pathology
Epidemiology
Disease
6 cases to date, children aged 6 months to 5 years, male
predominance; sex ratio 4M/2F.
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
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(9)
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.
Genetics
Note
Breakpoints difficult to ascertain in suboptimal
preparations.
761
t(X;11)(q13;q23)
Zamecnikova A
Fusion protein
Cytogenetics
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).
Probes
Pooled cDNA FISH-probes from AFX1: AFX 12, 115,
106, 108, 114.
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).
References
Smith JL, Clein GP, Barker CR, Collins RD. Characterisation of
malignant mediastinal lymphoid neoplasm (Sternberg
sarcoma) as thymic in origin. Lancet. 1973 Jan 13;1(7794):747
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.
Karpas A, Hayhoe FGJ, Greenberger JS, Barker CR, Cawley
JC, Lowenthal RM, Moloney WC.. The Establishment and
Cytological, Cytochemical and Immunological Characterisation
of Human Haemic Cell Lines: Evidence for Heterogeneity.
Leukaemia Res 1977; 1 : 35-49.
AFX1 (All-1 fusion partner on
chromosome X, MLLT7)
Nacheva E, Fischer P, Haas O, Manolova Y, Manolov G,
Levan A.. Acute myelogenous leukemia in a child with primary
involvement of chromosomes 11 and X. Hereditas.
1982;97(2):273-88.
Location
Xq13
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.
Pui CH, Raimondi SC, Murphy SB, Ribeiro RC, Kalwinsky DK,
Dahl GV, Crist WM, Williams DL.. An analysis of leukemic cell
chromosomal features in infants. Blood. 1987 May;69(5):128993.
Pui CH, Behm FG, Raimondi SC, Dodge RK, George SL,
Rivera GK, Mirro J Jr, Kalwinsky DK, Dahl GV, Murphy SB..
Secondary acute myeloid leukemia in children treated for acute
lymphoid leukemia. N Engl J Med. 1989 Jul 20;321(3):136-42.
Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr,
Williams DL.. Cytogenetics of childhood acute nonlymphocytic
leukemia. Cancer Genet Cytogenet. 1989 Jul 1;40(1):13-27.
MLL (Mixed lineage leukemia gene,
ALL1, HRX, and Hrtx)
Location
11q23
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.
Parry P, Wei Y, Evans G.. Cloning and characterization of the
t(X;11) breakpoint from a leukemic cell line identify a new
member of the forkhead gene family. Genes Chromosomes
Cancer. 1994 Oct;11(2):79-84.
Result of the chromosomal
anomaly
Harrison CJ, Cuneo A, Clark R, Johansson B, LafagePochitaloff M, Mugneret F, Moorman AV, Secker-Walker LM..
Ten novel 11q23 chromosomal partner sites. European 11q23
Workshop participants. Leukemia. 1998 May;12(5):811-22.
Hybrid gene
Kalla C, Nentwich H, Schlotter M, Mertens D, Wildenberger K,
Dohner H, Stilgenbauer S, Lichter P.. Translocation
t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia
disrupts two novel genes. Genes Chromosomes Cancer. 2005
Feb;42(2):128-43.
Bentz M, Huck K, du Manoir S, Joos S, Werner CA, Fischer K,
Dohner H, Lichter P.. Comparative genomic hybridization in
chronic B-cell leukemias shows a high incidence of
chromosomal gains and losses. Blood. 1995 Jun
15;85(12):3610-8.
Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J,
Hammermann J, Henn T, Lampert F.. Cloning and
characterization of AFX, the gene that fuses to MLL in acute
leukemias with a t(X;11)(q13;q23). Oncogene. 1997 Jan
16;14(2):195-202.
Note
5' MLL - AFX 3' as well as the 5' AFX - MLL 3'.
This article should be referenced as such:
Zamecnikova A. t(X;11)(q13;q23). Atlas Genet Cytogenet
Oncol Haematol. 2011; 15(9):761-762.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(9)
762