Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.

Pedersen‐Bjergaard, Jens; Sigsgaard, T.; Nielsen, Dorte; Gjedde, Susanne B.; Philip, Preben; Hansen, Mogens; Larsen, Severin Olesen; Rørth, Mikael; Mouridsen, Henning T.; Dombernowsky, P

doi:10.1200/jco.1992.10.9.1444

Cited by 123 publications

(44 citation statements)

References 35 publications

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“…Such mutations are important since they often appear to confer resistance to further anti-cancer treatment (Lowe et al, 1994;Wada et al, 1994;Aas et al, 1996). Loss or translocation of chromosomal material has been observed in the secondary tumours of human patients treated with epirubicin or the closely related drug doxorubicin (Pedersen-Bjergaard et al, 1992;Ho mann et al, 1995). This type of genetic damage is suggested to result from intercalation of the drug into DNA and inhibition of DNA topoisomerase II activity (Tewey et al, 1984;Bartkowiak et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

et al. 1998

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Section: Discussionmentioning

confidence: 99%

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

et al. 1998

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“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24] More recently, the DNA topoisomerase II inhibitors have also been shown to be leukemogenic, in most instances administered in combination with platinum derivatives or an alkylating agent. [25][26][27][28] These leukemias primarily present balanced translocations to chromosome bands 11q23 or 21q22 29 with rearrangement of the MLL and the AML1 genes, but also less frequently other balanced rearrangements such as the inv (16)(p13q22), and the t(15;17)(q22;q11) known from de novo MDS and AML. 30,31 The whole-arm translocations leading to dicentric chromosomes as observed in t-MDS and t-AML in the present study differ generally from the balanced chromosome aberrations.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

Andersen

Pedersen‐Bjergaard

2000

Leukemia

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Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

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“…This translocation is primarily a de novo, or idiopathic event, by the lack of identified causal exposure in most of the cases. T (8;21) occasionally occurs in leukemias associated with prior exposure to cancer chemotherapy of both alkylator and topoisomerase II inhibitor activity, 8,[25][26][27][28][29] and has also been reported in leukemias associated with certain occupational exposures. [30][31][32][33] AML1 is occasionally fused to other partners in therapy-related leukemias, including EVI-1/MDS/EAP, MTG16, and other partners in chromosomes 1, 12, 14 and others.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of genomic AML1-ETO fusions in childhood leukemia

et al. 2001

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T(8;21) AML1(CBFA2)-ETO(MTG8)is the most common chromosomal translocation in acute myeloid leukemia (AML) in both children and adults. We sought to understand the structure and gain insight into the fusion process between AML1 and ETO by sequencing genomic fusions in 17 primary childhood AMLs and two cell lines with t(8;21). Reciprocal translocations were sequenced for seven of the 19 samples. We assumed a null hypothesis that the translocation breakpoints would be evenly distributed along the intronic breakpoint cluster regions. Testing for multimodality via smoothed bootstrap statistical methods suggested, however, the presence of two separate cluster regions within both the AML1 and ETO breakpoint cluster regions. ETO breakpoints were predominantly located in intron 1B in a defined cluster 5Ј of exon 1A (scan statistic P value = 0.00001). All patients with available RNA expressed an AML1-ETO mRNA fusion between exon 5 of AML1 and exon 2 of ETO. Since the structural restraints for the fusion protein of AML1-ETO exclude exon 1A, we reason that ETO intron 1B harbors a structural feature with propensity for breakage and/or recombination. Chromosomal breakpoints displayed evidence of fusion by a non-homologous end joining process, with microhomologies and nontemplate nucleotides at some fusion junctions. Breakpoints in general displayed similar complexity of duplications, deletions, and insertions to other common pediatric leukemia translocations (TEL-AML1, MLL-AF4, PML-RARA, CBFB-MYH11) that we and others have analyzed. Leukemia (2001Leukemia ( ) 15, 1906Leukemia ( -1913

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Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.

Cited by 123 publications

References 35 publications

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

Molecular characterization of genomic AML1-ETO fusions in childhood leukemia

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