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Clinical Implications of Methotrexate Pharmacogenetics in Childhood Acute Lymphoblastic Leukaemia

[ Vol. 20 , Issue. 4 ]

Author(s):

Guillermo Gervasini* and Sonia Mota-Zamorano   Pages 313 - 330 ( 18 )

Abstract:


Background: In the past two decades, a great body of research has been published regarding the effects of genetic polymorphisms on methotrexate (MTX)-induced toxicity and efficacy. Of particular interest is the role of this compound in childhood acute lymphoblastic leukaemia (ALL), where it is a pivotal drug in the different treatment protocols, both at low and high doses. MTX acts on a variety of target enzymes in the folates cycle, as well as being transported out and into of the cell by several transmembrane proteins.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question.

Results: This review has intended to summarize the current knowledge concerning the clinical impact of polymorphisms in enzymes and transporters involved in MTX disposition and mechanism of action on paediatric patients with ALL.

Conclusion: In this work, we describe why, in spite of the significant research efforts, pharmacogenetics findings in this setting have not yet found their way into routine clinical practice.

Keywords:

Methotrexate, polymorphism, folate cycle, efficiency, toxicity, childhood acute lymphoblastic leukaemia.

Affiliation:

Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, Av. Elvas s/n 06006, Badajoz, Department of Medical & Surgical Therapeutics, Medical School, University of Extremadura, Av. Elvas s/n 06006, Badajoz

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