Emergence of translocation t(9;11)-positive leukemia during treatment of childhood acute lymphoblastic leukemia

✍ Scribed by Markus Metzler; Pamela L. Strissel; Reiner Strick; Charlotte Niemeyer; Silja Roettgers; Arndt Borkhardt; Jochen Harbott; Wolf D. Ludwig; Martin Stanulla; Martin Schrappe; Dirk Reinhardt; Ursula Creutzig; Joern D. Beck; Wolfgang Rascher; Reinald Repp; Thorsten Langer

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 115 KB
• Volume: 41
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.20083

✦ Synopsis

Abstract

Therapy‐related acute myeloid leukemia (t‐AML) characterized by the t(9;11)(p22;q23) translocation is one of the most frequent secondary malignancies. The timing of the initiation of translocation and of development of the malignant t(9;11) clone during chemotherapy is presently unknown. In the present study, we backtracked bone marrow samples from three children during treatment for acute lymphoblastic leukemia (ALL). Two patients developed a t(9;11)‐positive t‐AML 19 and 30 months after therapy start, whereas the third patient, diagnosed with a rare t(9;11)‐positive ALL, suffered from an ALL relapse 23 months after initial diagnosis. The genomic MLL–MLLT3 (MLL–AF9) fusion site was amplified by a multiplex, nested long‐range PCR and used as a clonal marker for quantification of the MLL–MLLT3‐positive cells during chemotherapy. The t(9;11)‐positive clone was detectable 13 and 18 months after therapy start in both t‐AML cases, which was 6–12 months before clinical diagnosis of the secondary malignancy. In the t(9;11)‐positive ALL patient, the identical leukemic clone reoccurred during maintenance therapy after a short molecular remission, 8 months before clinically overt ALL relapse. The time course and characteristics of the genomic breakpoints in the present t‐AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage. © 2004 Wiley‐Liss, Inc.