Absence of Mutations in the CDKN2 Binding Site of CDK4 in Childhood Acute Lymphoblastic Leukemia

• Published in: Leukemia & lymphoma 2001, Vol.40 (3-4), p.413-417
• Main Authors: Einsiedel, Hagen Graf V., Taube, Tillmann, Beyermann, Birgit, Dragon, Serge, Möricke, Anja, Kebelmann-betzig, Christian, Köchling, Joachim, Henze, GÜNter, Seeger, Karlheinz
• Format: Article
• Language: English
• Subjects: Binding Sites - genetics; Bone Marrow - pathology; Calibration; CDK4 gene; CDKN2 gene; Child; childhood ALL; cyclin dependent kinase inhibitor genes; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-Dependent Kinases - genetics; DNA Mutational Analysis; Genetic Testing; Humans; mutations; Point Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Proto-Oncogene Proteins; Tumor Cells, Cultured
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428190109057941

The cell cycle regulatory circuit resulting in phosphorylation of the retinoblastoma protein (pRB) is frequently altered in human cancers. Several mechanisms of disruption are known in that pathway. In childhood acute lymphoblastic leukemia (ALL), the main disrupting mechanism is the homozygous deletion of the CDKN2 (cyclin dependent kinase inhibitor 2) genes: p16CDKN2a p15CDKN2b and p19ARF Another pRB pathway disturbance is a previously described point mutation in the exon 2 of CDK4, a pRB phosphorylating enzyme, which abrogates binding of the latter to its inhibitors, p16CDKN2a and p15CDKN2b. Here we report the absence of point mutations in the CDKN2-binding site of CDK4 in 100 cases of childhood ALL, 2 cases of childhood chronic myeloid leukemia and 9 hematologic cell lines screened by PCR-SSCP (polymerase chain reaction single stranded conformational polymorphism gel electrophoresis), thereby minimizing the possibility of the existence of these specific CDK4 mutations in childhood ALL.