The translocation t(16;21) involving RUNXI (AMLI) and resulting in the RUNXI-CBFA2T3 fusion is a rare but recurrent abnormality mostly found in therapy-related acute myeloid leukemia (t-AML) associated with agents targeting topoisomerase II (topo II). We characterized, at the genomic level, the t(16;21) translocation in a patient who developed t-AML after treatment of multiple sclerosis with mitoxantrone (MTZ). Long template nested PCR of genomic DNA followed by direct sequencing enabled the localization of RUNXI and CBFA2T3 (ETO2) breakpoints in introns 5 and 3, respectively. Sequencing of the cDNA with specific primers showed the presence of the expected RUNXI-CBFA2T3 fusion transcript in leukemic cells. The RUNXI intron 5 breakpoint was located at nucleotide position 24,785. This region contained an ATGCCCCAG nucleotide sequence showing similar to 90% homology to a "hotspot" DNA region ATGCCCTAG present in intron 6 of PML previously identified in therapy-related acute promyelocytic leukemia cases arising following treatment with MTZ. This study suggests a wider distribution in the human genome, and particularly at genes involved in chromosome translocations observed in t-AML, of DNA regions (hotspot) targeted by specific topo II drugs. (c) 2008 Wiley-Liss, Inc.

Ottone T., H.S. (2009). Identification of a potential "Hotspot" DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation. GENES, CHROMOSOMES & CANCER, 48(3), 213-221 [10.1002/gcc.20633].

Identification of a potential "Hotspot" DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation

Noguera N. I.;AMADORI, SERGIO;LO COCO, FRANCESCO
2009

Abstract

The translocation t(16;21) involving RUNXI (AMLI) and resulting in the RUNXI-CBFA2T3 fusion is a rare but recurrent abnormality mostly found in therapy-related acute myeloid leukemia (t-AML) associated with agents targeting topoisomerase II (topo II). We characterized, at the genomic level, the t(16;21) translocation in a patient who developed t-AML after treatment of multiple sclerosis with mitoxantrone (MTZ). Long template nested PCR of genomic DNA followed by direct sequencing enabled the localization of RUNXI and CBFA2T3 (ETO2) breakpoints in introns 5 and 3, respectively. Sequencing of the cDNA with specific primers showed the presence of the expected RUNXI-CBFA2T3 fusion transcript in leukemic cells. The RUNXI intron 5 breakpoint was located at nucleotide position 24,785. This region contained an ATGCCCCAG nucleotide sequence showing similar to 90% homology to a "hotspot" DNA region ATGCCCTAG present in intron 6 of PML previously identified in therapy-related acute promyelocytic leukemia cases arising following treatment with MTZ. This study suggests a wider distribution in the human genome, and particularly at genes involved in chromosome translocations observed in t-AML, of DNA regions (hotspot) targeted by specific topo II drugs. (c) 2008 Wiley-Liss, Inc.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/15 - Malattie del Sangue
English
complementary DNA; cytarabine; DNA; fludarabine; genomic DNA; granulocyte colony stimulating factor; mitoxantrone; transcription factor RUNX1; acute granulocytic leukemia; adult; article; case report; chromosome translocation; DNA sequence; gene; gene fusion; gene identification; gene targeting; gene translocation; human; human genome; intron; leukemia cell; male; multiple sclerosis; nucleotide sequence; polymerase chain reaction; priority journal; RUNXI gene; sequence analysis; Core Binding Factor Alpha 2 Subunit; Cytogenetic Analysis; Databases, Genetic; DNA Topoisomerases, Type II; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Multiple Sclerosis; Oncogene Proteins, Fusion; Phosphoproteins; Repressor Proteins; Sequence Analysis, DNA; Translocation, Genetic; Tumor Suppressor Proteins
Ottone T., H.S. (2009). Identification of a potential "Hotspot" DNA region in the RUNXI gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation. GENES, CHROMOSOMES & CANCER, 48(3), 213-221 [10.1002/gcc.20633].
Ottone, T; Hasan, Sk; Montefusco, E; Curzi, P; Mays, An; Chessa, L; Ferrari, A; Conte, E; Noguera, Ni; Lavorgna, S; Ammatuna, E; Divona, M; Bovetti, K; Amadori, S; Grimwade, D; LO COCO, F
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/39417
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