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Abstract. Reciprocal chromosomal translocations are recurrentfeatures of many hematological malignancies. The cloning of thegenes located at the breakpoints of chromosomal translocationsin leukemia and lymphoma has led to the identification of newgenes involved in carcinogenesis. Molecular studies of thebreakpoint of several translocations involving chromosomal band11q23 led to the cloning of a gene that was named MLL. Basedon 7969 cases of acute myeloblastic leukemia (AML) and 1252cases of acute lymphoblastic leukemia (ALL) taken from theliterature, band 11q23 and/or the MLL gene was involved in5.2% of AML and 22% of ALL. Differences in the frequencyand the distribution of translocations were noted according to thetype of acute leukemia and age of the patients. Seventy-fivedifferent rearrangements involving band 11q23 have so far beenidentified, 39 MLL partner genes having been cloned. The fusionof MLL and its partner gene leads to a gain of function of theMLL gene. The accumulating data suggests that the fusionprotein affects the differentiation of the hematopoietic pluripotentstem cells or the lymphoid or myeloid committed stem cells byderegulating the HOX gene expression patterns.
Reciprocal chromosomal translocations are recurrent
features of many hematological malignancies. The cloning
of the genes located at the breakpoints of chromosomal
translocations in leukemia and lymphoma has led to the
identification of new genes involved in carcinogenesis.
These rearrangements mainly lead to the activation of a
proto-oncogene by relocation near active regulatory
sequences [t(11;14)(q13;q32) translocation in mantle cell
lymphoma for example] or the generation of a new gene,called fusion gene [for example t(15;17)(q22;q21) leading to
the PML-RAR· fusion gene] (1, 2). Most of these
rearrangements are unique in that they are identified in
specific leukemia and lymphoma subtypes and that they
involve two specific genes.
Molecular studies of the breakpoint of several
translocations involving chromosomal band 11q23 led to the
cloning of a gene that was named MLL (Mixed-Lineage
Leukemia or Myeloid-Lymphoid Leukemia) (3-8). This
gene is also known as ALL1, HTRX, HRX or TRX1.
MLL abnormalities can be divided in two categories. The
first category consists of MLL rearrangements, usually as
translocations or insertions, some of them cryptic, leading to
fusion genes with a large number of partners (9, 10). It will be
the focus of this review. In addition, self-fusion of two parts
of the MLL within the breakpoint cluster region (bcr), leading
to internal rearrangements called partial tandem duplication
(PTD), have also been described in several cases (11, 12). A
second category of abnormalities is the amplification of the
11q23 region leading to the presence of multiple copies of the
MLL gene, located either intrachromosomally as homo-
geneously staining region (hsr), or extrachromosomally in
double minutes (dmin) (13). Numerical abnormalities of
chromosome 11, such as trisomies or tetrasomies, also result
in additional copies of the MLL gene.
Despite the large variety of rearrangements involving the
MLL gene, the overall prognosis of acute myeloblastic
leukemia (AML) with this abnormality is unfavorable (14,
1931
Presented at the 7th International Conference of Anticancer
Research held in Corfu, Greece from October 25 - 30, 2004.
Correspondence to: Pr. Marc De Braekeleer, Laboratoire de
Cytogénétique, Faculté de Médecine et des Sciences de la Santé,
Université de Bretagne Occidentale, 22, avenue Camille Desmoulins,
CS 93837, F-29238 Brest cedex 3, France. Tel: + 33 (0)2 98 01 64 76,
Fax: + 33 (0)2 98 01 81 89, e-mail: [email protected]
Key Words: MLL gene, chromosomal band 11q23, acute leukemia.
ANTICANCER RESEARCH 25: 1931-1944 (2005)
Review
The MLL Gene and Translocations Involving Chromosomal Band 11q23 in Acute Leukemia
MARC DE BRAEKELEER1,2, FRÉDÉRIC MOREL1,2, MARIE-JOSÉE LE BRIS2,
ANGÈLE HERRY1 and NATHALIE DOUET-GUILBERT1,2
1Laboratoire d’Histologie, Embryologie et Cytogénétique, Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest;
2Service de Cytogénétique, Cytologie et Biologie de la Reproduction, CHU Morvan, Brest, France
0250-7005/2005 $2.00+.40
15). Therefore, detection of MLL disruption or
amplification is much needed for treatment decision.
Studying the wide variety of fusion genes involving MLLcould also lead to a better understanding of
leukemogenesis.
Distribution of rearrangements involving band11q23 and/or the MLL gene
Numerous studies have calculated the prevalence of
rearrangements of band 11q23 by banding cytogenetics and,
more recently, of the MLL gene by Southern blotting or
fluorescent in situ hybridization (FISH). Differences have
been noted between banding cytogenetics and the other
techniques. Indeed, Southern blotting and FISH are much
more sensitive and allow the recognition of rearrangements of
the MLL gene that are undetected by banding cytogenetics.
Furthermore, although the large majority of 11q23
translocations involves the MLL gene, a few cases of acute
leukemia not involving MLL have been described (16, 17).
A literature search allowed us to identify 7969 cases of
AML and 1252 cases of acute lymphoblastic leukemia (ALL)
that were studied for rearrangements of band 11q23 and/or
the MLL gene (References in Appendix 1). Overall, 5.2% of
AML and 22% of ALL have a translocation involving 11q23
or MLL. Their distribution by age groups shows 58.7% of
the AML and 67.6% of the ALL to have a rearrangement
among patients less than 1 year old (Figure 1). These
frequencies decline steadily among patients less or more
than 15 years old.
ANTICANCER RESEARCH 25: 1931-1944 (2005)
1932
Figure 1. Distribution of 11q23 translocations by age groups and type ofacute leukemia (based on 7969 cases of AML and 1252 cases of ALLfrom the literature).
Figure 4. Distribution of 11q23 translocations in AML by FAB subtypes(based on 3360 cases from the literature).
Figure 3. Distribution of some specific 11q23 translocations by age groupsand type of acute leukemia (based on 7969 cases of AML and 1252 casesof ALL from the literature).
Figure 2. Distribution of some specific 11q23 translocations by type ofacute leukemia (based on 7969 cases of AML and 1252 cases of ALLfrom the literature).
The t(4;11)(q21;q23) translocation is solely observed in
ALL patients and is present in 43.1% of the cases (Figure
2). The second most frequent translocation is
t(11;19)(q23;p13) in ALL (13%). In AML, t(9;11)(p21;q23)
is the most frequent translocation (18.6%). The
t(10;11)(p12;q23) is rare, but still present in 3.9% of AML
patients. A wider variety of other translocations than these
4 is observed in AML (14.7%) than in ALL (8.0%). The
distribution of translocations by type of acute leukemia and
age groups shows that the t(4;11) is almost exclusively
present in ALL infants (less than 1 year old) (Figure 3). In
AML, the frequency of t(9;11) increases with age, while
translocations other than t(4;11), t(9;11), t(10;11) and
t(11;19) are found in all age groups with similar frequencies.
Moreover, the distribution by FAB (French-American-
British) subtypes is available for 3360 of the 7969 AML
cases taken from the literature. Translocations involving
band 11q23 or the MLL gene are more likely to be found in
the M5 (24.9%) and M4 (8.8%) subtypes. No patient among
the 261 with M3 had a 11q23 rearrangement (Figure 4).
In 1998, the European Union Concerted Action
Workshop on 11q23 collected 550 cases of acute leukemia
and myelodysplastic syndromes with a rearrangement of
11q23 (18) (References in Appendix 2). This workshop
confirmed that the t(4;11) is the most frequent translocation
in ALL (68.1%), whereas the t(9;11) and other
translocations are mainly found in AML (41.2% and 14.8%,
respectively) (Figure 5).
De Braekeleer et al: MLL Gene and Acute Leukemia
1933
Figure 5. Distribution of some specific 11q23 translocations by type ofacute leukemia (based on 550 cases with an acquired abnormality of11q23 reported by the European Union Concerted Action Workshop on11q23 – Secker-Walker, 1998).
Figure 8. Distribution of some specific 11q23 translocations in FABsubtype AML-M5 (based on 550 cases with an acquired abnormality of11q23 reported by the European Union Concerted Action Workshop on11q23 – Secker-Walker, 1998).
Figure 6. Distribution of some specific 11q23 translocations by age groups(based on 550 cases with an acquired abnormality of 11q23 reported bythe European Union Concerted Action Workshop on 11q23 – Secker-Walker, 1998).
Figure 7. Distribution of some specific 11q23 translocations in AML byFAB subtypes (based on 550 cases with an acquired abnormality of 11q23reported by the European Union Concerted Action Workshop on 11q23 –Secker-Walker, 1998).
The distribution of translocations by age groups also
confirms that the t(4;11) is more frequent in infants (less
than 1 year old) (Figure 6), the t(9;11) being fairly equally
distributed among the different age groups and the other
translocations being more frequent after 1 year old. These
differences are partly explained by the preferential
association of some translocations with specific types of
acute leukemia that occur at different ages.
The distribution of the several translocations shows that the
t(9;11) is well represented in the different AML subtypes
ANTICANCER RESEARCH 25: 1931-1944 (2005)
1934
Figure 9. Example of translocation involving the MLL gene.
Figure 10. Exon structure of the MLL gene and location of the breakpoint cluster region (bcr).
(Figure 7). However, this may be misleading; as an example,
there was only one patient with M7. Again, no patient with M3
was found among the 550 patients with 11q23 translocations.
It should also be noted that the patients with M5a are more
likely to have a t(9;11) than patients with M5b, while other
translocations are more frequent in M5b patients (Figure 8).
More recently, Bloomfield et al. published a paper from
an international workshop on balanced chromosome
aberrations in treatment-related myelodysplastic syndromes
and acute leukemia (19). They collected 511 cases, of which
162 had a rearrangement of band 11q23 (31.7%). The
t(9;11) translocation was the most frequent (47.3%),
followed by t(11;19) (21.6%).
All these studies indicate that band 11q23 and the MLLgene are frequently rearranged in de novo and therapy-
related acute leukemia. Furthermore, although some genes
are the preferential partners in most cases, translocations
involving other partner genes are not uncommon (20, 21).
The MLL gene: structure and function
The MLL gene consists of at least 37 exons spanning over
100kb. Sequence analysis of cDNA showed an open reading
frame of some 12kb, encoding for a protein of 3969 amino
acids localizing to nuclear structures (22). Its protein
structure includes several domains (3, 15, 22-30): i) 3 AT
hooks motifs binding to the minor groove of DNA and
influencing the chromatin structure; ii) 1 transcriptional
repression domain including a cysteine-rich region (CxxC)
of homology with DNA methyltransferase, which is involved
in the epigenetic regulation of transcription by methylation
and 2 zinc-finger domains (PHD – plant homology domain)
involved in protein-protein interaction; iii) a
serine/threonine rich region acting as a trans-activator; iv)
a SET domain, in the C-terminal region, the function of
which could be to recruit chromatin remodelling complexes
to specific chromosomal regions
The MLL gene shares 3 regions of homology with the
Drosophila trithorax gene (TRX); these are the 2 zinc-finger
domains and the SET domain. In fact, the MLL gene is the
human homologue of the TRX gene, a member of a highly
conserved family of genes, which regulates the homeotic
gene complex (HOX) by maintaining the transcriptional
states in the later developmental stages (31). The TRXprotein is part of the TAC1 complex that also includes a
histone acetyltransferase (dCBP) and a SET-binding factor
(SEBF1) (32).
Similarly, the MLL protein is part of a larger complex of
at least 27 proteins, whose components are involved in
epigenetic regulation, notably nucleosome remodelling and
De Braekeleer et al: MLL Gene and Acute Leukemia
1935
Figure 11. MLL-partner fusion gene structure.
histone deacetylation and methylation (26, 28, 29). Through
direct physical interactions with DNA, MLL binds to
HOXA9 and HOXC8 promoters and regulates specific HOXtarget genes (28, 29, 33). The MLL gene is expressed at high
levels in differentiated myeloid cells, at low levels in stem
cells and lymphocytes, but not in erythrocytes (34, 35).
HOX genes are a major group of transcription factors,
playing a role in the early stages of development and
hematopoietic differentiation, as well as in the later stages
of hematopoietic differentiation with a specific pattern of
expression in different lineages at various differentiation
stages. They are down-regulated upon induction of terminal
differentiation, as the stem cell differentiates into mature
cells (36-39).
MLL fusion genes: structure, chromosome locationand function
Translocations involving band 11q23 usually lead to a
breakage in the MLL gene (Figure 9). The 5’ part of the
MLL gene is retained on the derivative chromosome 11
where it is fused with the 3’ part of the partner gene.
Therefore, the active fusion gene (5’ MLL-3’partner) is
almost always located in the der(11), except in rare cases of
insertion of the 5’ MLL in another chromosome (40).
The breakpoints within the MLL gene cluster in the 8.5kb
region, called the breakpoint cluster region (bcr) located
between exons 5 and 11 (Figure 10) (24, 27, 41, 42). This
leads to a "hot spot" hypothesis supported by the
identification of a cluster of ALU repetitive elements,
recombinase signal sequences, a number of scaffold
attachment regions (SAR) and topoisomerase II consensus
binding sites (25, 27, 43 - 45). The ALU sequences are
located in the centromeric part of bcr, while the
topoisomerase II binding consensus sites are located in the
telomeric portion of bcr. These topoisomerase II binding
consensus sites include 11 sequences closely related to
topoisomerase II consensus binding sites and a perfect
consensus binding site in exon 9 (44, 46).
Acute leukemia and myelodysplastic syndromes secondary
to previous chemotherapy for a primary tumor or leukemia
have a higher frequency of MLL rearrangements if the
ANTICANCER RESEARCH 25: 1931-1944 (2005)
1936
Figure 12. Distribution of the partners of 11q23 translocations or the MLL gene.
De Braekeleer et al: MLL Gene and Acute Leukemia
1937
Table I. MLL fusion partners: chromosome location and functions.
Name Chromosome Function Other
location names
AF1p 1p32 ·-helical coils EPS15
Probable EGF receptor tyrosine kinase substrate MLLT5
Putative signal transduction
AF1q 1q21 Growth factor
LAF4 2q11-2q12 Putative transcription activator MLLT2
AF3p21 3p21 SH3-containing protein NCK1PSD
Signal transduction?
GMPS 3q24 Cell division
Guanosine monoP synthetase
LPP 3q27-3q28 Putative signal transduction
AF4 4q21 Transcription activator MLLT2
FEL
FLJ10849 4q21 ?
AF5 5q12 Dimerization protein
AF5q31 5q31 Transcription activator
GRAF 5q31 Negative regulator of RhoA KIAA0621
GTPase activating protein for Rho OPHN1L
AF6q21 6q21 Transcription factor FKHRL1
Forkhead DNA binding FOXO3A
AF6 6q27 Signal transduction MLLT4
·-helical coils
CDK6 7q21 Cyclin-dependent kinase 6
AF9 9p22 Transcription activator MLLT3
LTG9
AF9q34 9q34 Negative regulator of RAS proteins activity DAB2IP
DIP1/2
KIAA1743
FBP17 9q34 Telomere maintenance KIAA0554
AF10 10p12 Transcription activator MLLT10
Leucine zipper
ABI1 10p11.2 Cell growth inhibitor E3B1
Signal transduction SSH3BP1
LCX 10q21 Zinc-binding CXXC domain TET1
Methyltransferase domain KIAA1676
CALM 11q14-11q21 Role in integration of signals from different pathways PICALM
CBL 11q23-11q25 Negative regulatory activity in protein CBL2
tyrosine kinase-mediated signaling pathways
therapeutic regimen contained topoisomerase II inhibitors
(epipodophyllotoxins such as etoposide and teniposide) (19,
47). The mechanism of action of the topoisomerase II
inhibitors (including bioflavonoids present in certain fruits
and vegetables, soybean, cocoa, tea, etc.) is still unclear.
Topoisomerase II is an ubiquitous enzyme that facilitates the
ANTICANCER RESEARCH 25: 1931-1944 (2005)
1938
Table I. continued.
Name Chromosome Function Other
location names
ARHGEF12 11q23.3 Rho guanine nucleotide exchange factor LARG
KIAA0382
CIP29 12q13 DNA transcription
GPHN 14q23.3 Gly-receptor associated protein GPHRYN
KIAA1385
AF15q14 15q14 Growth repressor
MPFYVE 15q14 Signal transduction?
CBP 16p13.3 Transcription coactivator CREBBP
Histone acetyltransferase activity RTS
RSTS
GAS7 17p13 Growth-arrest specific protein KIAA0394
AF17 17q21 Transcription factor MLLT6
MSF 17q25 Cell cycle regulation? AF17q25
Signal transduction? MSF1
Cytoskeleton organization KIAA0991
Putative GTP binding domain PNUTL4
SEPT9
LASP1 17q11-17q21.3 ? MLN50
LIM
SH3 protein 1
ENL 19p13.3 Transcription activator LTG19
MLLT1
EEN 19p13.3 ·-helical coils SH3GL1
Signal transduction?
ELL 19p13.1 Transcription elongation factor MEN
Regulation of cell growth and survival
hCDCRel-1 22q11.2 Cytoskeleton organization PNUTL1
Putative GTP binding domain CDCRel
AF22
P300 22q13.2 Transcription coactivator E1A
Histone acetyltransferase activity EP300
Cell differentiation
AFX1 Xq13 Transcription factor MLLT7
Forkhead DNA binding FOXO4
Septin 6 Xq22 Cytoskeleton organization KIAA0128
Cytokinesis Septin 2
unwinding of the DNA helix, allowing DNA replication and
transcription. The inhibitors may inhibit the ligase function
of the topoisomerase II enzyme, leaving DNA free ends that
can repair through non-homologous recombination between
the MLL and the partner genes (15, 44, 48-52).
The localization of the topoisomerase II binding
consensus sites in the telomeric portion of bcr may explain
why breakpoints in secondary leukemia and in infant
leukemia have a biased distribution towards the telomeric
portion of bcr, whereas breakpoints in adult de novoleukemia are randomly distributed within bcr (46). These
findings also raise the hypothesis that a maternal dietary
regime rich in bioflavonoids could be involved in
leukemogenesis in utero (51, 53, 54).
Fusion genes keep the AT hook domains and the
methyltransferase domain (transcriptional repression
domain) of MLL, but lack the activation domain and the
SET domain (Figure 11) (30, 42, 55-63). The fusion proteins
consist of the N-terminal portion of the MLL protein fused
to the C-terminal portion of a partner protein. Due to the
loss of the SET domain, histone methylation of the HOXA9and HOXC8 promoters cannot occur (28, 29). This induces
perturbations of HOX gene expression (64).
Partners of translocations involving band 11q23 or the
MLL gene have been localized on all the chromosomes
(Figure 12). A literature search till October 1st, 2004
enabled the recognition of 75 different rearrangements; 28
involving band 11q23 have not been proven to be associated
with a rearrangement of the MLL gene. In 8 different
translocations, fluorescent in situ hybridization showed split
signals of the MLL probe, signing a rearrangement of the
MLL gene. Thirty-nine MLL partner genes have been
identified (15, 25, 27, 30, 48, 53, 56, 65-69). They are
scattered in the whole karyotype. Different partner genes
are located in the same chromosomal band; for example,
AF9q34 and FBP17 are both located in band 9q34 and
ENL, EEN and ELL in band 19p13.
The function, sometimes still putative, of the partners
thus far identified is shown in Table I (42, 56-63, 66). Most
of the MLL partner proteins are distributed in two classes.
Some are transcription and transcription regulator factors,
while others participate in transduction signaling.
The fusion of MLL and its partner gene leads to a gain of
function of the MLL gene (53, 70-73). Two mechanisms have
been proposed. Fusion with nuclear partners having a
transcriptional activation activity induces an increased
transcriptional activation; these fusions are characterized by
a short latency and occur in infant and therapy-related acute
leukemia (for example: AF4, AF9, AF10, ENL). Fusion with
cytoplasmic partners can induce dimerization of MLL, which
results in an increased transcriptional activation; these
fusions are characterized by a longer latency and occur in
adult acute leukemia (for example: AF1p, AF6, EEN).
The MLL fusion genes usually occur in tumors of specific
hematological lineages, leading to the hypothesis that the
MLL partner plays a critical role in determining the disease
phenotype (for example: MLL-AFX1 in T-ALL, MLL-AF4
in B lineage ALL, MLL-EEN in AML, MLL-ENL in
ALL/AML) (66). This suggests that the fusion protein
affects the differentiation of the hematopoietic pluripotent
stem cells or the lymphoid or myeloid committed stem cells.
However, the HOX gene expression patterns appear to be
similarly deregulated, independently of the nature of the
fusion partner gene (64, 74-76).
Several functional consequences of MLL fusion proteins
are known (15, 34, 42, 68, 77-80). MLL fusion proteins can
interfere with cell survival regulation by immortalizing the
committed stem cells and/or by meddling in the apoptosis
process. They can also modify the function of specific
transcription factors controlling myeloid differentiation and
even stop the process. They can disrupt signaling pathways,
notably by interfering with chromatin remodeling.
The hematopoietic pluripotent stem cell alone has the
capability of self-renewal. It gives rise to a multipotent
progenitor having both lymphoid and myeloid potential,
which, in turn, leads to progenitors of lymphoid cells and of
trilineage myeloid cells that are committed to differentiate
into the various blood cells.
Several hypotheses can be formulated (15, 81-85). The
MLL fusion gene is supposedly generated in the
hematopoietic pluripotent stem cell. It could immortalize an
early progenitor cell having both lymphoid and myeloid
potential. It could also induce commitment to a given pathway
(lymphoid or myeloid) followed by differentiation arrest.
Finally, it could stay silent until the transcription programs
that are normally regulated by the MLL gene become active at
a specific differentiation stage in a specific lineage.
In conclusion, much still needs to be learnt about the
function of the MLL gene and its fusion partner genes. This
endeavor will be a major step in understanding normal
hematopoietic development and leukemogenesis.
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Molecular rearrangements of the MLL gene are present in most
cases of infant acute myeloid leukemia and are strongly correlated
with monocytic or myelomonocytic phenotypes. J Clin Invest 93:
429-437, 1994.
43 Takeuchi J, Ohshima T and Amaki I: Cytogenetic studies in adult
acute leukemias. Cancer Genet Cytogenet 4: 293-302, 1981.
44 Taki T, Ida K, Bessho F, Hanada R, Kikuchi A, Yamamoto K,
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Appendix 2
References of the European Union Concerted Action Workshop on
11q23 used for the calculation of the prevalence of rearrangements
of band 11q23.
1 Bain BJ, Moorman AV, Johansson B, Mehta AB, Secker-Walker
LM and on behalf of the European 11q23 Workshop participants:
Myelodysplastic syndromes associated with 11q23 translocations.
Leukemia 12: 834-839, 1998.
2 Harbott J, Mancini M, Verellen-Dumoulin C, Moorman AV,
Secker-Walker LM and on behalf of the European 11q23
Workshop participants.: Hematological malignancies with a
deletion of 11q23: cytogenetic and clinical aspects. Leukemia 12:
823-827, 1998.
3 Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff
M, Mugneret F, Moorman AV, Secker-Walker LM and on behalf
of the European 11q23 Workshop participants: ten novel 11q23
chromosomal partner sites. Leukemia 12: 811-822, 1998.
4 Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL,
Swanton S, Secker-Walker LM and on behalf of the European
11q23 Workshop participants: Hematologic malignancies with
t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic
and clinical study of 183 cases. Leukemia 12: 779-787, 1998.
5 Johansson B, Moorman AV, Secker-Walker LM and on behalf of
the European 11q23 Workshop participants: Derivative
chromosomes of 11q23-translocations in hematologic malignancies.
Leukemia 12: 828-833, 1998.
6 Lillington DM, Young BD, Berger R, Martineau M, Moorman
AV, Secker-Walker LM and on behalf of the European 11q23
Workshop participants: The t(10;11)(p12;q23) translocation in
acute leukaemia: a cytogenetic and clinical study of 20 patients.
Leukemia 12: 801-804, 1998.
7 Martineau M, Berger R, Lillington DM, Moorman AV, Secker-
Walker LM and on behalf of the EU Concerted Action 11q23
Workshop participants: The t(6;11)(q27;q23) translocation in
acute leukemia: a laboratory and clinical study of 30 cases.
Leukemia 12: 788-791, 1998.
8 Moorman AV, Hagemeijer A, Charrin C, Rieder H, Secker-
Walker LM and on behalf of the EU Concerted Action 11q23
Workshop participants: The translocations, t(11;19)(q23;p13.1)
and t(11;19)(q23;p13.3); a cytogenetic and clinical profile of 53
patients. Leukemia 12: 805-810, 1998.
9 Secker-Walker LM, Moorman AV, Bain BJ, Mehta AB and on
behalf of the EU Concerted Action 11q23 Workshop: Secondary
acute leukemia and myelodysplastic syndrome with 11q23
abnormalities. Leukemia 12: 840-844, 1998.
10 Secker-Walker LM and on behalf of the European 11q23
Workshop participants: General report on the European Union
Concerted Action Workshop on 11q23, London, UK, May 1997.
Leukemia 12: 776-778, 1998.
11 Swansbury GJ, Slater R, Bain BJ, Moorman AV, Secker-Walker
LM and on behalf of the European 11q23 Workshop participants:
Hematological malignancies with t(9;11)(p21-22;q23) – a laboratory
and clinical study of 125 cases. Leukemia 12: 792-800, 1998.
Received December 28, 2004Accepted February 23, 2005
ANTICANCER RESEARCH 25: 1931-1944 (2005)
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