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May 1998, Volume 12, Number 5, Pages 828-833
Table of contents    Previous  Abstract  Next   Article  PDF
European union concerted action workshop on 11q23
Derivative chromosomes of 11q23-translocations in hematologic malignancies
B Johansson1, A V Moorman2 and L M Secker-Walker2

1Department of Clinical Genetics, Lund University Hospital, Sweden

2Department of Haematology, The Royal Free Hospital School of Medicine, London, UK

Abstract

Cytogenetic and molecular analyses of 11q23/MLL positive hematologic malignancies show that der(11) encodes the critical 5'MLL/3'partner gene transcript. The role of der(non-11) bearing the 5'partner/3'MLL fusion is less certain. The cytogenetic evidence for der(11) as the critical partner was investigated. Among 1680 cases (550 workshop and 1130 published) 31 cases displayed a three-way (29 cases) or four-way (two cases) translocation and 26 had only one of the derivatives. The critical junction created by t(11;n)(q23;n) was seen in all six cases of t(1;11)(q21;q23), in both cases of t(6;11)(q27;q23), in all six cases of t(11;19)(q23;p13), in nine of 11 cases with t(4;11)(q21;q23) and in 17 of 20 cases with t(9;11)(p21-22;q23). These findings support the evidence for der(11) encoding the critical leukemogenic fusion transcript. In contrast, additional change involving duplication of one of the derivatives resulted in duplication only of the non-critical der(non-11) as follows: +der(4)t(4;11)(q21;q23) [9/553], +der(6)t(6;11)(q27;q23) [3/61], +der(9)t(9;11)(p21-22;q23) [5/291] and +der(19)t(11;19)(q23;p13) [6/164]. A literature search of other neoplastic disorders showed that either derivative may be duplicated. Duplication of the non-critical derivative is the norm in AML patients with t(8;21)(q22;q22) or t(15;17)(q22;q12-21). We suggest that the genomic imbalance, rather than over-expression of the non-critical 5'partner/3'MLL, is likely to be the important outcome.

Keywords

11q23; derivative chromosome; hematologic malignancy

Received 12 December 1997; accepted 20 January 1998
May 1998, Volume 12, Number 5, Pages 828-833
Table of contents    Previous  Abstract  Next   Article  PDF