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Perforin A91V polymorphism and putative susceptibility to hematological malignancies

Leukemia volume 20, page 2178 (2006)Cite this article

We read with interest the article by Mehta PA et al.1 in Leukemia (2006). Although approximately 30% mutations in perforin gene are associated with familial hemophagocytic lymphohistiocytosis (HLH), the perforin A91V substitution has been shown to result only in a reduced natural killer cell and cytotoxic T lymphocytes cytotoxicity.2 However, recently some reports have linked perforin A91V substitution to confer increased susceptibility to childhood acute lymphoblastic leukemia3 (ALL) and lymphoma.4 But Mehta PA et al.1 could not substantiate this, in a large cohort of B-precursor childhood ALL. This prompted us to study perforin A91V in our population of childhood ALL and lymphoma patients.

The study population included 52 children with de novo childhood ALL, (Pediatric Oncology Group Classification) enrolled at our center over the past 5 years and nine patients with Non-Hodgkin's Lymphoma (NHL). Concurrently, 100 normal voluntary blood donors were also selected to determine the genotype frequencies from the same ethnic population to be used as controls. Genomic DNA was isolated from peripheral blood lymphocytes and the exons 2 and 3 of the perforin (PRF1) coding region was amplified using standard polymerase chain reaction (PCR). PCR products were then purified and sequenced in ABI 3100 DNA sequencer (Applied Biosystems, Foster City, CA, USA).

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References

  1. Mehta PA, Davis SM, Kumar A, Devidas M, Lee S, Zamzow T et al. Perforin polymorphism A91V and susceptibility to B-precursor childhood acute Lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia 2006; 20: 1539–1541.

    Article  CAS  Google Scholar 

  2. Trambas C, Gallo F, Pende D, Marcenaro S, Moretta L, De Fusco C et al. A single amino acid change, A91V, leads to conformational changes that can impair processing the active form of perforin. Blood 2005; 106: 932–937.

    Article  CAS  Google Scholar 

  3. Santora A, Cannella S, Trizzino A, Lo Nigro L, Corsello G, Arico M . A single amino acid change A91V in perforin: a novel, frequent predisposing factor to childhood acute lymphoblastic leukemia? Hematologica 2005; 90: 697–698.

    Google Scholar 

  4. Clementi R, Locatelli F, Dupre L, Garaventa A, Emmi L, Bregni M et al. A proportion of patients with lymphoma may harbour mutations of the perforin gene. Blood 2005; 105: 4424–4428.

    Article  CAS  Google Scholar 

  5. Busiello R, Fimiani G, Miano MG, Arico M, Santoro A, Ursini MV et al. A91V perforin variation in healthy subjects and FHLH patients. Int J Immunogenet 2006; 33: 123–125.

    Article  CAS  Google Scholar 

  6. Al Lamki Z, Wali YA, Pathare A, Erickson KG, Henter JI . Clinical and genetic studies of familial hemophagocytic lymphohistiocytosis in Oman: need for early treatment. Pediatr Hematol Oncol 2003; 20: 603–609.

    Article  Google Scholar 

  7. Muralitharan S, Al Lamki Z, Dennison D, Christie BS, Wali YS, Zachariach M et al. An inframe perforin gene deletion in familial hemophagocytic lymphohistiocytosis is associated with perforin expression. Am J Hematol 2005; 78: 59–63.

    Article  CAS  Google Scholar 

  8. Murlitharan S, Romana M, Al Maamari S, Al Said B, Al Maamari A, Zachariach M et al. Familial haemophagocytic lymphohistiocytosis in the Sultanate of Oman: two novel perforin gene variants. Blood 2002; 100 (Suppl b): 51b (Abstract 3669).

    Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman

    S Muralitharan

  2. Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman

    Y Wali

  3. Department of Haematology, Sultan Qaboos University Hospital, Muscat, Oman

    A V Pathare

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  1. S Muralitharan
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  2. Y Wali
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  3. A V Pathare
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Correspondence to A V Pathare.

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Muralitharan, S., Wali, Y. & Pathare, A. Perforin A91V polymorphism and putative susceptibility to hematological malignancies. Leukemia 20, 2178 (2006). https://doi.org/10.1038/sj.leu.2404433

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