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Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Leukaemia Section
Mini Review
t(1;11)(p32;q23)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: September 2010
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t0111p32q23ID1046.html
DOI: 10.4267/2042/45042
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
Identity
Clinics and pathology
Disease
Acute lymphoblastic leukaemia (ALL),
biphenotypic acute leukaemia (BAL), acute myeloid
leukaemia (AML), and myelodysplastic syndrome
(MDS).
Note
36 cases are available to date (Kaneko et al.,1986;
Gregoire et al., 1987; Selypes and Laszlo, 1987;
Hagemeijer et al., 1987; Hayashi et al., 1989; Raimondi
et al., 1989; Shippey et al., 1989; Pui et al., 1990;
Lampert et al., 1991; Abshire et al., 1992; Bernard et
al., 1994; Felix et al., 1995; Felix et al., 1998; Harrison
et al., 1998; Laughlin et al., 1998; Pinto et al., 1998;
Secker-Walker et al., 1998; Nakamura et al., 2000; von
Bergh et al., 2000; Chessells et al., 2002; Kim et al.,
2002; Tsujioka et al., 2003; Douet-Guilbert et al., 2005;
Sagawa et al., 2006; Jeon and Yi, 2009; de Braekeleer
et al., 2010; Shinohara et al., 2010); we have excluded
from this review a case of t(1;6;11)(p32;q21;q23) in a
T-cell lymphoma referred as "T-CLL", as it probably
represents another entity (Mecucci et al., 1988). We
must also keep in mind that some of the
t(1;11)(p32;q23) above harvested may not all share the
common genetic event 5' MLL - 3' EPS15: a case of
t(1;11)(p32;q23), del(5q), +8 in a patient with therapyrelated leukaemia has recently been described without
MLL rearrangement (Yamamoto et al., 2010). There
are also 3 paediatric cases (2 ALLs, 1 AML) of
MLL/EPS15 translocation which were not included in
this study, due to the lack of clinical data (Meyer et al.,
2006).
t(1;11)(p32;q23) G-banding - Courtesy Melanie Zenger and
Claudia Haferlach.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(6)
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t(1;11)(p32;q23)
Huret JL
Phenotype/cell stem origin
About half cases were ALLs and half cases AMLs.
There were 17 ALLs, (mainly CD19+, CD10-) 2
biphenotypic leukaemias, 15 AMLs (of which were
three M4-AMLs and nine M5-AMLs), and two MDS.
There were at least nine cases of secondary leukaemia
(and also 3 cases of "relapse", but each time with a
different karyotype; e.g. a M1-AML with the classical
t(8;21)(q22;q22) relapsed 16 months later with a
t(1;11) as the sole anomaly (Hayashi et al., 1989)). The
delay before onset of the secondary leukaemia including the so-called relapses- was very similar, from
a case to another, with a median of 16-21 months
(range 12-24 months), if we exclude a case with an
interval of 46 years after nuclear bombing (Nakamura
et al., 2000). The previous disease was a
haematological malignancy in seven cases (MDS,
AML, ALL, multiple myeloma, non Hodgkin
lymphoma (NHL)), a soft tissue tumour in three cases
(primitive neuroectodermal tumour (PNET), PEComa,
osteogenic sarcoma), and a breast cancer. The second
leukaemia was an ALL in 6 cases, and a myeloid
leukaemia (MDS or AML) in 6 cases.
Prognosis
Median survival was 15 months (see figure), with a
very few long survivors (a patient was still alive 140
months after diagnosis (Chessells et al., 2002)). Median
survival for female patients was 28 months, vs 11
months in male patients; Survival was significantly
different according to the sex of the patients (chi2 =
4,66, p < 0.05, log rang test at 16 months). Survival
curves for ALL and AML cases cross each other, with
a median survival at 28 months for ALL cases and only
14 months for AML cases, but with no statistical
significance. There was no correlation between age of
the patient and survival. All the same and more
surprisingly, the few patients with a secondary
leukaemia with data on survival (n=6) did not seem to
behave more badly than de novo cases. Also, the
presence or the absence of chromosomal anomalies
additional to the t(1;11) did not seem to affect the
prognosis.
Epidemiology
There was 12 male and 23 female patients (non
significant: epsilon = 1.86, 0.07 < p < 0.06). However,
while there was 8 male and 10 female patients in
myeloid cases, there was only 3 male patients and 13
female patients with ALL (chi2 = 6.25 p < 0.02).
Patients median age was 4 years (range 0-76 years);
thirteen cases (38%) were infant cases (at or under 1
year of age), seven cases (20%) were between 1 and 10
years, three cases between 10 and 16, and twelve cases
(1/3) were adult cases. Median age was 7 years in
myeloid cases versus 1 year in lymphoid cases (ranges
were 0.2-76 years and 0-63 years respectively, but with
5 cases and 1 case above 60 years respectively). About
half of female cases (11/23), but only 2 of 11 male
cases were congenital leukaemias (diagnosis at or
before one year of age), although the ranges were
similar, with cases above the sixties in both genders
this is not statistically significant (chi2 = 2.77, 0.05 < p
< 0.10). Median age in female patients was 2-3 years vs
7 years for male patients, ranges were similar.
Cytogenetics
Cytogenetics morphological
The t(1;11) was the sole anomaly in 19 of 33
documented cases (57%), equally distributed between
ALL and AML cases. There was two complex (three
way) translocations: a t(1;11;4)(p32;q23q13;p16) and a
t(1;11;10)(p32;q23;q24) (Selypes and Laszlo, 1987; de
Braekeleer et al., 2010).
Clinics
Additional anomalies
A high white blood cound was noted in 9 of 11
documented cases.
A trisomy 8 was found in four cases, a trisomy 21 in
two cases, a del(5q) or a monosomy 7 in one case each.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(6)
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t(1;11)(p32;q23)
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Karyotypes were similar in ALL and myeloid cases,
apart from that trisomy 8 was found as an
accompanying anomaly in 3 myeloid and only one
lymphoid cases, and that the cases with either del(5q)
or -7 were found in myeloid cases. A complex
karyotype was present in two myeloid cases.
complex; they form a multiprotein complex with
transcription factor TFIID. General transcription factor;
maintains HOX genes expression in undifferentiated
cells. Major regulator of hematopoiesis and embryonic
development; role in cell cycle regulation.
Genes involved and proteins
Result of the chromosomal
anomaly
EPS15 (epidermal growth factor
receptor pathway substrate 15)
Hybrid gene
Description
Variable breakpoint in MLL; fusion of exon 6 to 10 of
MLL to exon 2 of EPS15 in most studied cases; in one
case the fusion exon of EPS15 was exon 12, but it also
retains the coiled-coil domain of EPS15; in other cases,
the breakpoint is upstream exon 1.
Location
1p32
Protein
A major transcript of 5225 bp produces a 896 amino
acids protein from 25 exons; at least 5 other splice
variants from 30 different exons. Contains from N-term
to C-term: 3 EH (Eps15 Homology) domains (proteinprotein interaction modules) with calcium-binding
domains (EF hand domains), binding sites to adaptins,
SH3 binding site, prolin-rich motifs, ubiquitin
interacting motifs (UIM), and a nuclear export signal in
C-term. There are also DPF repeats in the C-term third
of the protein. Membrane receptor tyrosine kinase
signaling inhibition is accomplished by ligand/receptor
complexes internalization, subsequent trafficking to
lysosomes and ubiquitination. EPS15 is involved in this
process. EPS15 has a role in clathrin-mediated
endocytosis, and may also have a role in transcriptional
regulation (review in van Bergen and Henegouwen,
2009).
Fusion protein
Oncogenesis
The coiled-coil domains of EPS15 mediates
oligomerization, activating MLL, and MLL-EPS15
activates Hox gene expression (So et al., 2003).
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Atlas Genet Cytogenet Oncol Haematol. 2011; 15(6)
This article should be referenced as such:
Huret JL. t(1;11)(p32;q23). Atlas Genet Cytogenet Oncol
Haematol. 2011; 15(6):529-532.
532