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Acute Leukemias

Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group

Leukemia volume 20, pages 1539–1541 (2006)Cite this article

Abstract

Perforin plays a key role in the cytotoxicity of natural killer and cytotoxic T cells. Genetic mutations in the perforin gene (PRF1) give rise to approximately 30% cases of familial hemophagocytic lymphohistiocytosis. A frequent polymorphism, A91V (C to T transition at position 272), may impair processing of perforin protein to the active form, and has been suggested to increase susceptibility to childhood acute lymphoblastic leukemia (ALL). To investigate the role of A91V in ALL, we genotyped 2272 children with de novo ALL registered on the Pediatric Oncology Group ALL Classification study P9900 and 655 normal controls. Allele frequencies in the controls showed a very low frequency of the variant allele in blacks, 0.7% compared to 4% in white controls. In light of this, analysis was restricted to a comparison of white cases and controls only. Overall genotype frequencies were similar in white ALL cases and normal white controls (P=0.58), indicating that in contrast to the previous report, A91V polymorphism is not associated with increased risk of childhood ALL. PRF1 A91V frequency was significantly increased in children with BCR-ABL positive ALL (24 vs 8.5%; P=0.0048); however, this observation includes a relatively small number of cases and needs further exploration.

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Acknowledgements

This work was supported by: RO1 CA 935502-01, COG Grant CA 98543 and POG Grant CA 30969. Grants from Histiocytosis Associations of America and Canada. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG Grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

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Authors and Affiliations

  1. Division of Hematology Oncology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA

    P A Mehta, S M Davies, S Lee, T Zamzow, J Elliott, J Villanueva, Y Zewge & A Filipovich

  2. Pediatric Hematology Oncology, University of Minnesota, Minneapolis, MN, USA

    A Kumar

  3. Children's Oncology Group and Department of Epidemiology & Health Policy Research, Statistics, University of Florida, Gainesville, FL, USA

    M Devidas

  4. Pediatric Hematology Oncology, University of Mississippi, Jackson, MS, USA

    J Pullen

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  1. P A Mehta
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  2. S M Davies
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  3. A Kumar
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  4. M Devidas
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  5. S Lee
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  8. J Villanueva
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  10. Y Zewge
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  11. A Filipovich
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Correspondence to P A Mehta.

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Mehta, P., Davies, S., Kumar, A. et al. Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia 20, 1539–1541 (2006). https://doi.org/10.1038/sj.leu.2404299

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