Genetic susceptibility to therapy-related leukemia after Hodgkin lymphoma or non-Hodgkin lymphoma: role of drug metabolism, apoptosis and DNA repair

Ding, Yuan Chun; Cl, Sun; L, Li; M, Li; Francisco, Liton; Sabado, Melanie; Hahn, Bettina; Gyorffy, Janelle; J, Noe; Gp, Larson; Forman, Scott; Bhatia, Ravi; Bhatia, Smita

doi:10.1038/bcj.2012.4

Cited by 14 publications

(11 citation statements)

References 13 publications

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“…The homozygous T allele of C677T conferred and increased risk (p <0.001) when combined with the Pro carrier of P72R (conferring decreased apoptotic activity) compared to its combination with homozygous Arg. 87 …”

Section: Pathogenesismentioning

confidence: 99%

Therapy-Related Myelodysplasia and Acute Myeloid Leukemia

Bhatia

2013

Seminars in Oncology

164

116

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Therapy-related leukemia (t-MDS/AML) is a well known complication of conventional chemoradiotherapy used to treat a variety of primary malignancies including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), sarcoma, and ovarian and testicular cancer. The median time to development of t-MDS/AML is 3 to 5 years, with the risk decreasing markedly after the first decade. t-MDS/AML is the major cause of non-relapse mortality after autologous hematopoietic cell transplantation (HCT) for HL or NHL. The magnitude of risk of t-MDS/AML is higher, and the latency is shorter after HCT, compared to conventional therapy. Two types of t-MDS/AML are recognized depending on the causative therapeutic exposure: an alkylating agent/radiation-related type and a topoisomerase II inhibitor-related type. Interindividual variability in the risk for development of t-MDS/AML suggests a role for genetic variation in susceptibility to genotoxic exposures. Treatment of t-MDS/AML with conventional therapy is associated with a uniformly poor prognosis, with a median survival of 6 months. Because of the poor response to conventional chemotherapy, allogeneic HCT is recommended. Current research is focused on developing risk prediction and risk reduction strategies.

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Section: Pathogenesismentioning

confidence: 99%

Therapy-Related Myelodysplasia and Acute Myeloid Leukemia

Bhatia

2013

Seminars in Oncology

164

116

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“…12 Somatic mutations of TP53 are more common in tAML than in de novo AML, and tAML samples typically have lower expression of TP53. 13,14 Hypermethylation of the BRCA1 promoter is also more common in tAML than in de novo AML. 15 There is also evidence of increased DNA damage in tAML cells, including microsatellite instability, a sign of DNA damage that is rare in de novo AML.…”

Section: Introductionmentioning

confidence: 99%

Caspase-9 is required for normal hematopoietic development and protection from alkylator-induced DNA damage in mice

Lu¹,

McLellan²,

et al. 2014

Blood

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“…An association has been observed between the MTHFR haplotype and the risk of t‐MDS/AML among patients with breast cancer or hematologic malignancies who were exposed to alkylating agents or topo II inhibitors . Furthermore, a synergistic effect between TP53 and MTHFR has been reported: Expression levels of both TP53 and MTHFR were significantly lower in cases compared with controls, supporting their role in t‐MDS/AML development.…”

Section: Introductionmentioning

confidence: 91%

Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors

Bhatia

2014

Cancer

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Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat the primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk, and can possibly explain the observed inter-individual variability. This article provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs. This article also discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as, an appropriate study design, identification of an adequately sized study population together with a reliable plan for collecting and maintaining high quality DNA, clinical validation of the phenotype, and selection of an appropriate approach or platform for genotyping. Understanding the modifiers of risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care of cancer survivors.

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Genetic susceptibility to therapy-related leukemia after Hodgkin lymphoma or non-Hodgkin lymphoma: role of drug metabolism, apoptosis and DNA repair

Cited by 14 publications

References 13 publications

Therapy-Related Myelodysplasia and Acute Myeloid Leukemia

Therapy-Related Myelodysplasia and Acute Myeloid Leukemia

Caspase-9 is required for normal hematopoietic development and protection from alkylator-induced DNA damage in mice

Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors

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