title: Myeloprotection by cytidine deaminase gene transfer in antileukemic therapy.
abstract: Gene transfer of drug resistance (CTX-R) genes can be used to protect the hematopoietic system from the toxicity of anticancer chemotherapy and this concept recently has been proven by overexpression of a mutant O(6)-methylguaninemethyltransferase in the hematopoietic system of glioblastoma patients treated with temozolomide. Given its protection capacity against such relevant drugs as cytosine arabinoside (ara-C), gemcitabine, decitabine, or azacytidine and the highly hematopoiesis-specific toxicity profile of several of these agents, cytidine deaminase (CDD) represents another interesting candidate CTX-R gene and our group recently has established the myeloprotective capacity of CDD gene transfer in a number of murine transplant studies. Clinically, CDD overexpression appears particularly suited to optimize treatment strategies for acute leukemias and myelodysplasias given the efficacy of ara-C (and to a lesser degree decitabine and azacytidine) in these disease entities. This article will review the current state of the art with regard to CDD gene transfer and point out potential scenarios for a clinical application of this strategy. In addition, risks and potential side effects associated with this approach as well as strategies to overcome these problems will be highlighted.
authors.affiliation: Research Group Reprogramming, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Lachmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brennig
authors.forename: Ruhi
authors.initials: R
authors.lastname: Phaltane
authors.forename: Michael
authors.initials: M
authors.lastname: Flasshove
authors.forename: Dagmar
authors.initials: D
authors.lastname: Dilloo
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D038042:Myelopoiesis / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D003564:Cytidine Deaminase