title: Mu class glutathione S-transferase mRNA isoform expression in acute lymphoblastic leukaemia.
abstract: Glutathione S-transferases (GSTs) are implicated in cytotoxic drug resistance in leukaemia. In a previous study, expression of mu class GST (GSTM) was associated with poor prognosis in childhood acute lymphoblastic leukaemia (ALL), however, that study did not differentiate between individual GSTM isoforms. This study, therefore, investigated individual GSTM isoform expression in ALL blasts at the mRNA level. Leukaemic blasts from 21 children with ALL were studied. Interindividual variation in the pattern of GSTM mRNA isoform expression was demonstrated. GSTM2 transcript was expressed in all patients in contradistinction to GSTM5, which was not detected in any sample. GSTM3 and GSTM4 expression varied between individuals, with GSTM3 expressed in 62% and GSTM4 in 24% of patients. Lymphoblast expression of GSTM3 was positively related to good prognosis whereas expression of GSTM4 was not related to clinical outcome in this small cohort. No relationship was demonstrated with established indicators of prognosis, including sex, age, immunophenotype and presenting white cell count. The results suggest that expression of GSTM3 may play a role in determining prognosis in childhood ALL and could provide more information for accurate stratification of treatment. Further studies are required to determine whether there is a causal relationship between GSTM3 expression and clinical outcome.
authors.affiliation: Department of Paediatric Oncology, University of Bristol, UK. Pamela.kearns@bristol.ac.uk
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Kearns
authors.forename: Zofia M A
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Anjo
authors.initials: A
authors.lastname: Veerman
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hall
mesh_terms: D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000276:immunology / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D005982:Glutathione Transferase; C416969:glutathione transferase M3-3