Loss of heterozygosity of p16 correlates with minimal residual disease at the end of the induction therapy in non-high risk childhood B-cell precursor acute lymphoblastic leukemia.
We evaluated the incidence of MTS1/p16 deletions by loss of heterozygosity (LOH) analysis in 36 non-high risk B-cell precursor childhood acute lymphoblastic leukemia (BCP-ALL) and correlated these results with clinical features and with the presence of minimal residual disease (MRD) at the end of induction therapy. LOH was analyzed using three microsatellite markers flanking the p16 gene. MRD was studied by the polymerase chain reaction (PCR) for IgH and TCRdelta genes. All patients were classified and treated according to the BFM-86 protocol. A slower response to the induction treatment (MRD) was associated with LOH of p16 and worse clinical outcome. Thus, LOH of p16 may be a marker of chemotherapy resistance among the children classified as non-high risk BCP-ALL.
Department of Genetics, Hospital de Parapléjicos, Toledo, Spain.
Olga
O
Tutor
Miguel A
MA
Díaz
Manuel
M
Ramírez
Patricia
P
Algara
Luis
L
Madero
Pedro
P
Martínez
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D019942:Genes, p16; D006801:Humans; D007223:Infant; D015993:Life Tables; D019656:Loss of Heterozygosity; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D018895:Microsatellite Repeats; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate