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

Publication ,  Journal Article
Leung, W; Neale, G; Behm, F; Iyengar, R; Finkelstein, D; Kastan, MB; Pui, C-H
Published in: Cancer Epidemiol
June 2010

BACKGROUND: 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 (alphabetaT cells and CD45RO+/RA- memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (gammadeltaT 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 Vbeta 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.

Duke Scholars

Published In

Cancer Epidemiol

DOI

EISSN

1877-783X

Publication Date

June 2010

Volume

34

Issue

3

Start / End Page

303 / 308

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Time
  • Thymus Gland
  • T-Lymphocytes
  • Survivors
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oncology & Carcinogenesis
  • Lymphopenia
  • Immunity, Innate
  • Humans
 

Citation

APA
Chicago
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MLA
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Leung, W., Neale, G., Behm, F., Iyengar, R., Finkelstein, D., Kastan, M. B., & Pui, C.-H. (2010). Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia. Cancer Epidemiol, 34(3), 303–308. https://doi.org/10.1016/j.canep.2010.03.008
Leung, Wing, Geoffrey Neale, Fred Behm, Rekha Iyengar, David Finkelstein, Michael B. Kastan, and Ching-Hon Pui. “Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia.Cancer Epidemiol 34, no. 3 (June 2010): 303–8. https://doi.org/10.1016/j.canep.2010.03.008.
Leung W, Neale G, Behm F, Iyengar R, Finkelstein D, Kastan MB, et al. Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia. Cancer Epidemiol. 2010 Jun;34(3):303–8.
Leung, Wing, et al. “Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia.Cancer Epidemiol, vol. 34, no. 3, June 2010, pp. 303–08. Pubmed, doi:10.1016/j.canep.2010.03.008.
Leung W, Neale G, Behm F, Iyengar R, Finkelstein D, Kastan MB, Pui C-H. Deficient innate immunity, thymopoiesis, and gene expression response to radiation in survivors of childhood acute lymphoblastic leukemia. Cancer Epidemiol. 2010 Jun;34(3):303–308.
Journal cover image

Published In

Cancer Epidemiol

DOI

EISSN

1877-783X

Publication Date

June 2010

Volume

34

Issue

3

Start / End Page

303 / 308

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Time
  • Thymus Gland
  • T-Lymphocytes
  • Survivors
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Oncology & Carcinogenesis
  • Lymphopenia
  • Immunity, Innate
  • Humans