In:
Genes, Chromosomes and Cancer, Wiley, Vol. 41, No. 3 ( 2004-11), p. 291-296
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1045-2257
,
1098-2264
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2004
ZDB Id:
1018988-9
ZDB Id:
1492641-6
SSG:
12