Involvement of the MLL gene in T-lineage acute lymphoblastic leukemia

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.