Analysis of Vgamma/Jbeta trans-rearrangements in paediatric patients undergoing chemotherapy.
The frequency of the hybrid Vgamma/Jbeta trans-rearrangement in peripheral blood lymphocytes (PBLs) was analysed in a transversal study of paediatric patients (n = 210) with acute lymphoblastic leukaemia (ALL) and solid tumours (ST). Different amounts of DNA were used as the template for a nested polymerase chain reaction to evaluate the frequency of hybrid Vgamma/Jbeta genes, using silver-stained gels. The frequency of the rearrangement was evaluated in groups before, during and after therapy. A greatly increased frequency of Vgamma/Jbeta trans-rearrangement was found in PBLs of both groups of patients during exposure to chemotherapeutic agents compared with patients before chemotherapy. In patients who had finished treatment, the frequency of the rearrangement fell promptly to the baseline levels in ST but showed a slow decrease in ALL in those in whom increased levels could be found until 4 years after the end of treatment. We hypothesize that the chemotherapeutic agents are able to induce the Vgamma/Jbeta trans-rearrangement, but this is transient in most cases. The exact relationship between the persistence of the rearrangement and the occurrence of secondary leukaemia remains to be determined.
Lopes
L F
LF
Centro de Tratamento e Pesquisa Hospital do Cancer, Ludwig Institute for Cancer Research, São Paulo, Brazil. lf.lopes@sti.com.br
Dias Neto
E
E
Lorand-Metze
I
I
Latorre
M R
MR
Simpson
A J
AJ
D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D004591:Electrophoresis, Polyacrylamide Gel; D005500:Follow-Up Studies; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005819:Genetic Markers; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000235:genetics; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000235:genetics; D013997:Time Factors
D018943:Anthracyclines; D005819:Genetic Markers