Inactivation of the p15 gene in children with acute lymphoblastic leukemia.
BACKGROUND
Tumor suppressor genes act on the control of cell cycle progression. In pediatric neoplasias, some of these genes may be considered to be markers for diagnosis or relapse, thus probably representing prognostic indicators.


OBJECTIVE
To study the inactivation of the p15 gene in children with acute lymphoblastic leukemia.


METHODS
Retrospective study.


METHODS
Laboratory of Molecular Biology, Department of Pediatrics, Faculdade de Medicina de Ribeiráo Preto, Universidade de São Paulo.


METHODS
Eighty-three children and adolescents with acute lymphoblastic leukemia were studied, with the examination of 83 bone marrow samples obtained at diagnosis, four obtained also during relapse, and two cerebrospinal fluid samples obtained from two cases of isolated relapse in the central nervous system.


METHODS
Homologous deletion of the p15 gene by multiplex polymerase chain reaction, and screening for point mutations by polymerase chain reaction/single-strand conformational polymorphism.


RESULTS
Deletion of exon 2 of the p15 gene was observed in 15 children, including one case in which deletion was only verified during isolated central nervous system relapse. No case of exon 1 deletion, or that was suggestive of point mutations, was observed and no association between p15 gene inactivation and classic risk factors was established.


CONCLUSIONS
According to the literature, inactivation of the p15 gene by deletion of exon 2 in acute lymphoblastic leukemia found in the population studied would be considered to be a molecular marker for diagnosis or relapse. However, no correlation between p15 gene deletion and clinical prognostic indicators was observed.
Cipolotti
Rosana
R
Department of Pediatrics, Faculdade de Medicina de Ribeiráo Preto, Universidade de São Paulo, Ribeiráo Preto, São Paulo, Brazil.
Lemos
José Alexandre Rodrigues
JA
Defavery
Ricardo
R
Scrideli
Carlos Alberto
CA
Dal Fabbro
Amaury Lellis
AL
Tone
Luiz Gonzaga
LG
D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins