Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia.

Purpose: Asparaginase (ASNase) is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia (ALL), but it is also associated with several toxicities.

Experimental Design: We recently reported the results of an association study between ASNase pathway genes and event-free survival (EFS) in childhood patients with ALL. The same polymorphisms were interrogated here in relation to allergies, pancreatitis, and thrombotic events following treatment with E.

Bim polymorphisms: influence on function and response to treatment in children with acute lymphoblastic leukemia.

Purpose: Corticosteroids induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies showed major implication of proapoptotic Bim in mediating corticosteroid-related resistance in leukemia cells.

Experimental Design: We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding.

Role of NOS3 DNA variants in externalizing behavioral problems observed in childhood leukemia survivors.

Objective: Neuropsychological problems occurrence varies among childhood cancer survivors, and associated risk factors have not been fully deciphered. We wanted to study the role of genetic variants in behavioral problems in this population.

Study Design: Behavioral problems in pediatric acute lymphoblastic leukemia patients (n=138) were investigated longitudinally, using the Child Behavior Checklist questionnaire and multilevel statistical modeling.

RGS5 gene and therapeutic response to short acting bronchodilators in paediatric asthma patients.

Short-acting β2-adrenergic receptor agonists are commonly used bronchodilators for symptom relief in asthmatics. Recent evidence demonstrated that prolonged exposure of cultured airway smooth muscle cells to β2 agonists directly augments procontractile signaling pathways with the change in expression of regulator of G protein signaling 5 (RGS5). The aim of this study was to test whether genetic variants in RGS5 gene affect the response to short acting β2-agonists.

ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia.

Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome.

Phosphodiesterase type 4D gene polymorphism: association with the response to short-acting bronchodilators in paediatric asthma patients.

Short-acting b2-adrenergic receptor agonists are commonly used bronchodilators for symptom relief in asthmatics. The aim of this study was to test whether genetic variants in PDE4D gene, a key regulator of b2-adrenoceptor-induced cAMP turnover in airway smooth muscle cells, affect the response to short-acting b2-agonists. Bronchodilator responsiveness was assessed in 133 asthmatic children by % change in baseline forced expiratory volume in one second (FEV(1)) after administration of albuterol.

Suggestive evidence for a new locus for epilepsy with heterogeneous phenotypes on chromosome 17q.

Purpose: To characterize the clinical features and molecular genetic background in a family with various epilepsy phenotypes including febrile seizures, childhood absence epilepsy, and possible temporal lobe epilepsy.

Methods: Clinical data were collected. DNA and RNA were extracted from peripheral blood.

Polymorphisms in glucocorticoid receptor gene and the outcome of childhood acute lymphoblastic leukemia (ALL).

Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms -627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p=0.

Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia.

Methotrexate and 6-mercaptopurine, important components of acute lymphoblastic leukemia treatment, are substrates for multidrug resistance-associated protein MRP4. Eight single nucleotide polymorphisms were analyzed in MRP4 gene, and 4 variants were identified as tagSNPs with frequency more than or equal to 5%. They were investigated for association with treatment responses in 275 children with acute lymphoblastic leukemia.

Variants of the KCNMB3 regulatory subunit of maxi BK channels affect channel inactivation.

The steady-state and kinetic properties of the KCNMB3 regulatory subunits associated with calcium-activated potassium channels (BK channels) are presented. BK channels containing four sequence variants (V1-V4) in the four different isoforms of the beta-subunit (beta3a, beta3b, beta3c, and beta3d) were expressed in Xenopus oocytes. Reconstituted BK channel inactivation ranged from none to around 90% inactivation.