title: Do alpha deletions influence hydroxyurea response in thalassemia intermedia?
abstract: Thalassemia intermedia patients show variable phenotypes. Hydroxyurea (HU) may benefit some of the thalassemia intermedia cases (1), however, the parameters influencing the response to HU have not been reported. In this study, the molecular parameters, alpha-globin and beta-globin genotype and the Xmn I polymorphism, were correlated with the HU response. Twenty patients with thalassemia intermedia were given HU (10-20 mg/kg) and responses were evaluated over a one year period. Twelve patients (60%) showed a good response to therapy with a significant increase in Hb and HbF levels and with elimination of the transfusion requirement in four patients. Four out of the twelve (33%) patients were positive for -alpha(3.7) deletions whereas none of the 8 non-responders were positive for alpha deletions. One each of the responders and non-responders were positive for alpha alpha alpha(anti-3.7) triplication. Three (25%) responsive and one non-responsive patients were homozygous for the IVS1-1 (G-->T) mutation. Three of the responsive patients with alpha deletions were also homozygous positive for Xmn I polymorphism. Thus, in addition to acting in synergy with the XmnI polymorphism, alpha deletions may be an independent factor predicting good response to HU in thalassemia intermedia, although this needs to be confirmation in larger studies.
authors: Department of Hematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors: I
authors: I
authors: Panigrahi
authors: A
authors: A
authors: Dixit
authors: S
authors: S
authors: Arora
authors: M
authors: M
authors: Kabra
authors: M
authors: M
authors: Mahapatra
authors: V P
authors: VP
authors: Choudhry
authors: R
authors: R
authors: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011110:Polymorphism, Genetic; D011379:Prognosis; D017384:Sequence Deletion; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics*
chemical_list: D005914:Globins; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific; D006918:Hydroxyurea