Although genome-wide analyses have identified somatic alterations contributing to the pathogenesis of pediatric acute lymphoblastic leukemia (ALL), few studies have identified germline variants conferring risk of this disease. Two reports now provide the first genome-wide glimpse into the role of inherited alleles in ALL pathogenesis.
"This allows application of genomic strategies similar to those used in humans such as subclassification of tumors according to gene expression patterns . Furthermore, naturally occurring DNA polymorphisms can help identify variants that influence lymphoma development or progression, thereby providing genetic clues for understanding disease biology . An additional advantage is that canine lymphomas are an excellent model of chemoresistant disease. "
[Show abstract][Hide abstract] ABSTRACT: Cancer stem cell (CSC) research has increased exponentially, because the outcome could provide further insight into the mechanisms of both carcinogenesis and chemotherapy resistance. This study was performed to explore the potential value of side population assay for the identification and characterization of putative CSCs in canine lymphoma cells. Canine lymphoma cells from cell lines and clinical samples were subjected to the side population (SP) assay which comprised of Hoechst 33342 dye staining and subsequent flow cytometric analysis. The SP assay revealed various amounts of SP fraction in the canine lymphoma cells, although the SP percentages were not affected by inhibitors of membrane transporters, verapamil hydrochloride and fumitremorgin C. Most of the canine lymphoma cells expressed high level of Bmi-1 and membrane transporter proteins, such as ABCG2 and p-glycoprotein. This study laid the groundwork for the further studies of biological behaviors and molecular characteristics of CSCs in canine lymphoma.
[Show abstract][Hide abstract] ABSTRACT: During the past decade, array CGH has been applied to study copy number alterations in the genome in human leukemia in relation to prediction of prognosis or responsiveness to therapy. In the first segment of this review, we will focus on the identification of acquired mutations by array CGH, followed by studies on the pathogenesis of leukemia associated with germline genetic variants, phenotypic presentation and response to treatment. In the last section, we will discuss constitutional genomic aberrations causally related to myeloid leukemogenesis.
Cytogenetic and Genome Research 08/2011; 135(3-4):260-70. DOI:10.1159/000330629 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Childhood acute lymphoblastic leukemia (ALL), a heterogeneous disease that includes multiple subtypes is defined by cell lineage and chromosome anomalies. Previous genome-wide association studies have reported several ARID5B and IKZF1 single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. High-resolution melting (HRM) analysis is a rapid and convenient technique to detect SNPs; we thereby detected SNPs in ARID5B and IKZF1 genes.
We enrolled 79 pediatric ALL patients and 80 healthy controls. Polymorphic variants of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs7073837, rs10740055, and rs7089424) were detected by HRM, and SNPs were analyzed for association with childhood ALL.
The distribution of genotype rs7073837 in ARID5B significantly differed between ALL and controls (P=0.046), while those of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs10740055 and rs7089424) did not. We analyzed the association for SNPs with B lineage ALL to find rs7073837 in ARID5B, conferring a higher risk for B lineage ALL (odds ratio, OR=1.70, 95% confidence interval, CI=1.01-2.87, P=0.049).
HRM is a practical method to detect SNPs in ARID5B and IKZF1 genes. We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL.
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