Translocations involving 11q23 are considered synonymous with rearrangements of the MLL gene. They are usually associated with B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia but have also been reported in T-lineage ALL.1-6Although most can be identified by routine cytogenetic analysis, their prognostic importance means that molecular methods are frequently employed to ensure detection.

Recently, Hayette et al7 reported the results of screening 81 patients with T-ALL for the involvement of the MLL gene using Southern blotting, reverse transcriptase–polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). They reported that 4 of 47 (8%) adults and 0 of 34 children had a rearrangement of the MLL gene. Using molecular methods, 3 cases with a del(11)(q23) by cytogenetics were found to have a t(6;11)(q27;q23), while the other case had a cryptic t(10;11)(p12;q23) with no cytogenetically visible 11q23 abnormality. These observations led Hayette et al to recommend the routine screening of all adults with T-ALL for MLL abnormalities.

The EU Concerted Action Workshop on 11q23 reported 9 patients with T-ALL and an established 11q23 translocation, with molecular techniques confirming the involvement of the MLL gene in 4 cases. The series comprised 3 cases of t(11;19)(q23;p13.3);1 2 of t(10;11);2 and one each of t(4;11)(q21;q23),3 t(6;11),4t(9;11)(p21∼22;q23),5 and t(11;17)(q23;q21).6 The age of these patients spanned from 3 months to 49 years and consisted of 2 infants (younger than 1 year), 3 children (15 years or younger), and 4 adults.

Since 1998 the Leukaemia Research Fund (LRF) UK Cancer Cytogenetics Group (UKCCG) Karyotype Database in ALL8 has been screening patients entered into the Medical Research Council (MRC) ALL treatment trials for abnormalities of the MLL gene by interphase FISH. Currently, a total of 210 patients with T-ALL have been screened using commercially available probes: the LSI MLL probe (Vysis, United Kingdom) or the MLL DNA probe (Appligene Oncor, United Kingdom). Overall, rearrangements of the MLL gene were found in 10 (5%) cases. The incidence among children and adults was very similar—7 of 159 (4%) and 3 of 51 (6%), respectively. Six cases had a t(11;19), of which 5 were also observed by G-banded cytogenetic analysis. The remaining 4 cases had cytogenetically visible rearrangements of 11q23, which have not yet been fully characterized. Unfortunately, the follow-up time on these 10 cases is too short to be informative.

Clearly, 11q23/MLL translocations are a recurrent feature of both adult and childhood T-ALL. Although most major 11q23 translocations have been reported in T-ALL, the results from this study and a recent international collaboration9 suggest that t(11;19) may be associated with T-ALL. Traditionally, 11q23 abnormalities have been associated with a poor outcome,10,11 however, recent studies suggest that the worst prognosis is restricted to older adults and infants.3,9 Assessing the prognostic significance of 11q23/MLL abnormalities within the context of T-ALL, which is also an indicator of poor prognosis and itself not independent of age,12 will be difficult. Furthermore, the prognostic relevance of different 11q23 translocations has yet to be determined. Therefore, we would strongly recommend screening all subtypes of ALL at all ages for 11q23/MLL abnormalities.

References

References
1
Moorman
AV
Hagemeijer
A
Charrin
C
Rieder
H
Secker-Walker
LM
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
1998
805
810
2
Lillington
DM
Young
BD
Martineau
M
Berger
R
Moorman
AV
Secker-Walker
LM
The t(10;11)(p12;q23) translocation in acute leukemia: a cytogenetic and clinical profile of 20 patients.
Leukemia.
12
1998
801
804
3
Johansson
B
Moorman
AV
Haas
OA
et al. 
Hematologic malignancies with t(4;11)(q21;q23)—a cytogenetic, morphologic, immunophenotypic, and clinical study of 183 cases.
Leukemia.
12
1998
779
787
4
Martineau
M
Berger
R
Lillington
DM
Moorman
AV
Secker-Walker
LM
The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases.
Leukemia.
12
1998
788
791
5
Swansbury
GJ
Slater
R
Bain
BJ
Moorman
AV
Secker-Walker
LM
Hematological malignancies with t(9;11)(p21–22;q23)—a laboratory and clinical study of 125 cases.
Leukemia.
12
1998
792
800
6
Harrison
CJ
Cuneo
A
Clark
R
et al. 
Ten novel 11q23 chromosomal partner sites.
Leukemia.
12
1998
811
822
7
Hayette
S
Tigaud
I
Maguer-Satta
V
et al. 
Recurrent involvement of the MLL gene in adult T-lineage acute lymphoblastic leukemia.
Blood.
99
2002
4647
4649
8
Harrison
CJ
Martineau
M
Secker-Walker
LM
The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group karyotype database in acute lymphoblastic leukaemia: a valuable resource for patient management.
Br J Haematol.
113
2001
3
10
9
Pui
CH
Gaynon
PS
Boyett
JM
et al. 
Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region.
Lancet.
359
2002
1909
1915
10
Secker-Walker
LM
Prentice
HG
Durrant
J
Richards
S
Hall
E
Harrison
G
Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA: MRC Adult Leukaemia Working Party.
Br J Haematol.
96
1997
601
610
11
Chessells
JM
Swansbury
GJ
Reeves
B
Bailey
CC
Richards
SM
Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X.
Br J Haematol.
99
1997
93
100
12
Hann
I
Vora
A
Harrison
G
et al. 
Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol.
Br J Haematol.
113
2001
103
114