Related Experiment Video
Updated: Jul 27, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from
P A Mehta1, S M Davies, A Kumar
1Division of Hematology Oncology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA. parinda.mehta@ccmhc.org
Insights
The perforin A91V gene variant does not increase childhood acute lymphoblastic leukemia (ALL) risk overall. However, it was found more frequently in children with BCR-ABL positive ALL, warranting further investigation.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- Perforin is crucial for natural killer and cytotoxic T cell function.
- PRF1 gene mutations cause familial hemophagocytic lymphohistiocytosis.
- The PRF1 A91V polymorphism may affect perforin processing and has been linked to childhood acute lymphoblastic leukemia (ALL) susceptibility.
Purpose of the Study:
- To investigate the association between the PRF1 A91V polymorphism and childhood de novo acute lymphoblastic leukemia (ALL).
Main Methods:
- Genotyping of 2272 children with de novo ALL and 655 normal controls.
- Analysis restricted to white cases and controls due to population-specific allele frequencies.
- Comparison of genotype frequencies between ALL cases and controls.
Main Results:
- No significant association was found between the PRF1 A91V polymorphism and overall childhood ALL risk in white populations (P=0.58).
- The PRF1 A91V allele frequency was significantly higher in children with BCR-ABL positive ALL compared to controls (24% vs 8.5%, P=0.0048).
Conclusions:
- The PRF1 A91V polymorphism is not associated with an increased risk of childhood ALL.
- A potential association between PRF1 A91V and BCR-ABL positive ALL requires further research due to the small sample size.
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.
Related Concept Videos
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase