A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia.

Abstract

Little is known about alterations of cyclin dependent kinase inhibitors p15INK4B, p16INK4A and of MDM2 inhibitor p14ARF due to single nucleotide polymorphisms (SNPs) located within the CDKN2A/B genes and/or neighbouring loci. In order to investigate the potential involvement of such common DNA sequence variants in leukemia susceptibility, an association study was performed by genotyping 23 SNPs spanning the MTAP, CDKN2A/B and CDKN2BAS loci, as well as relative intergenic regions, in a case-control cohort made up of 149 leukemia patients, including Philadelphia positive (Ph(+)) acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) samples, and 183 healthy controls. rs564398, mapping to the CDKN2BAS locus that encodes for ANRIL antisense non-coding RNA, showed a statistically significant correlation with the ALL phenotype, with a risk pattern that was compatible with an overdominant model of disease susceptibility and a OR of 2 (95% CI, 1.20-3.33; p=7.1×10(-3)). We hypothesized that this association reflects the capability of some ANRIL polymorphisms to contribute to its transcription changes responsible for alterations of CDKN2A/B expression profiles, thus leading to abnormal proliferative boosts and consequent increased ALL susceptibility.

• Authors: Ilaria Iacobucci, Marco Sazzini, Paolo Garagnani, Anna Ferrari, Alessio Boattini, Annalisa Lonetti, Cristina Papayannidis, Vilma Mantovani, Elena Marasco, Emanuela Ottaviani, Simona Soverini, Domenico Girelli, Donata Luiselli, Marco Vignetti, Michele Baccarani, Giovanni Martinelli
• Journal: Leukemia research (Leuk Res) Vol. 35 Issue 8 Pg. 1052-9 (Aug 2011) ISSN: 1873-5835 [Electronic] England
• PMID: 21414664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Cyclin-Dependent Kinase Inhibitor p15
• Cyclin-Dependent Kinase Inhibitor p16
• DNA, Neoplasm
• RNA, Untranslated

Topics

• Adolescent
• Adult
• Aged
• Case-Control Studies
• Chromosomes, Human, Pair 9 (genetics)
• Cohort Studies
• Cyclin-Dependent Kinase Inhibitor p15 (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• DNA, Neoplasm (genetics)
• Female
• Follow-Up Studies
• Humans
• Leukemia, Myeloid, Acute (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics)
• RNA, Untranslated (genetics)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Young Adult