title: Impact of Topoisomerase II alpha and spermine on the clinical outcome of children with acute lymphoblastic leukemia.
abstract: It has been reported in the literature that a leukemic cell may be (or become) resistant to anti-cancer treatment because many mechanisms, such as efflux membrane pump (multi-drug resistance, MDR-P170), intracellular transport (LRP, MRP), or different detoxification systems (glutathione transferases, methallothioneines) may be implicated. Topoisomerase II alpha (TopoII) are also reported as responsible for resistance since their main action is to repair DNA breakage. Polyamines are described as having a protective DNA action by stabilizing the double stranded DNA helix. For these reasons we investigated 65 children with acute lymphoblastic leukemia using an immunocytochemical method to elucidate the potential role of Topoisomerase and polyamines in drug resistance. Most children (60/65) were treated with the French (acute lymphoblastic leukemia, ALL) protocol (FRALLE-93) in which B and C arms include (at least) VP16. Children with cytoplasmic TopoII positivity (18 cases) were more resistant since their overall survival was 34 months compared to more than 110 months for negative cases ( P = 0.0003). Polyamines may be associated with drug resistance since the overall survivals were 51 months and 92 months for positive and negative patients, respectively, but the P-value is only 0.13. We conclude that Topoisomerase and polyamines must be tested at diagnosis as new possible markers for chemo-resistance. Larger series are needed to confirm these preliminary results and to verify if the use of anti epipodophillotoxin agents (as it is the case for FRALLE B or C) should be excluded for positive cases.
authors.affiliation: Laboratoire d'Hematologie, Hopital SUD, 16 Boulevard de Bulgarie, 35056 Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grandgirard
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ly-Sunnaram
authors.forename: Dominique
authors.initials: D
authors.lastname: Ferrant
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Christine
authors.initials: C
authors.lastname: Edan
authors.forename: Edouard
authors.initials: E
authors.lastname: Le Gall
authors.forename: Jacques-Phillipe
authors.initials: JP
authors.lastname: Moulinoux
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leray
authors.forename: Jean E
authors.initials: JE
authors.lastname: Goasguen
mesh_terms: D000951:Antigens, Neoplasm; D002648:Child; D003593:Cytoplasm / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D013096:Spermine / Q000032:analysis*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D013096:Spermine; D004250:DNA Topoisomerases, Type II