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Article: Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia

TitleDeficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia
Authors
KeywordsImmunity
Second malignancy
Children
Lymphoblastic leukemia
DNA damage
Issue Date2010
Citation
Cancer Epidemiology, 2010, v. 34, n. 3, p. 303-308 How to Cite?
AbstractBackground: Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Methods: Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. Results: In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (αβT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (γδT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vβ spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. Conclusion: ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. © 2010 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/294435
ISSN
2020 Impact Factor: 2.984
2020 SCImago Journal Rankings: 1.156
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, Wing-
dc.contributor.authorNeale, Geoffrey-
dc.contributor.authorBehm, Fred-
dc.contributor.authorIyengar, Rekha-
dc.contributor.authorFinkelstein, David-
dc.contributor.authorKastan, Michael B.-
dc.contributor.authorPui, Ching Hon-
dc.date.accessioned2020-12-03T08:22:44Z-
dc.date.available2020-12-03T08:22:44Z-
dc.date.issued2010-
dc.identifier.citationCancer Epidemiology, 2010, v. 34, n. 3, p. 303-308-
dc.identifier.issn1877-7821-
dc.identifier.urihttp://hdl.handle.net/10722/294435-
dc.description.abstractBackground: Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Methods: Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. Results: In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (αβT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (γδT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO-/RA+ naïve T cell and less SjTREC levels in the blood, whereas the Vβ spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole-genome scanning by SNP microarray analysis. Conclusion: ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. © 2010 Elsevier Ltd. All rights reserved.-
dc.languageeng-
dc.relation.ispartofCancer Epidemiology-
dc.subjectImmunity-
dc.subjectSecond malignancy-
dc.subjectChildren-
dc.subjectLymphoblastic leukemia-
dc.subjectDNA damage-
dc.titleDeficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.canep.2010.03.008-
dc.identifier.pmid20413363-
dc.identifier.pmcidPMC2874127-
dc.identifier.scopuseid_2-s2.0-77952241296-
dc.identifier.volume34-
dc.identifier.issue3-
dc.identifier.spage303-
dc.identifier.epage308-
dc.identifier.isiWOS:000279148300014-
dc.identifier.issnl1877-7821-

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