Korean J Hematol 1998; 33(3):
Published online September 30, 1998
© The Korean Society of Hematology
권정아, 이갑노
적십자병원 임상병리과,
고려대학교 의과대학 임상병리학교실
Background: The CDK4I(cyclin dependent kinase 4 inhibitor) gene is on the chromosome 9p21. It encodes p16, which binds to CDK4, and inhibits phosphorylation of retinoblastoma protein(pRb) by D-type cyclin-CDK4 complex. D-type cyclin-CDK4 complex phosphorylates pRb which regulates transition of G1 to S phase of the cell cycle. So inactivation of the CDK4I gene leads to the dysregulation of the cell cycle and may contribute to the malignant progression of cells. Homozygous deletion of CDK4I gene was frequently found in human hematologic malignancies. The purpose of this study is to find the relationship between the CDK4I gene homozygous deletion and diverse acute leukemia.
Methods: We analyzed homozygous deletions of the CDK4I gene from 21 cases of acute leukemia by means of Southern blot analysis(10 B-cell acute Iymphocytic leukemias, 6 T-cell acute Iymphocytic leukemias, 5 acute myelogenous leukemias). Hybridization of EcoRI digested DNA using CDK4I probes(exon 1 and exon 2) obtained by PCR of human control DNA was performed.
Results:
1) We observed 4 cases(19%) of homozygous deletions in 21 cases of acute leukemia. 2) ALL 4 cases of homozygous CDK4I deletion were T-cell ALL which
accounted for 66%(4/6 cases) of T-cell ALLs. 3) Homozygous CDK4I deletions were not found in any cases of B-ALLs(0/10 cases) and AML(0/5 cases). 4) In 4 cases of homozygous deletion consistent results were obtained by 2 different CDK4I probes (pv 336-bp probe, pv 142-bp probe)
Conclusion: The high frequency of CDK4I homozygous deletions in T-ALLs supports that the inactivation of these genes plays an important role in the pathogenesis of
T-ALL.
Keywords CDK4I; p16; Acute leukemia; Southern blot analysis;
Korean J Hematol 1998; 33(3): 322-333
Published online September 30, 1998
Copyright © The Korean Society of Hematology.
권정아, 이갑노
적십자병원 임상병리과,
고려대학교 의과대학 임상병리학교실
Jueng Ah Kwon, Kap No Lee
Department of Clinical Pathology, Seoul Red Cross Hospital
Department of Clinical Pathology, College of Medicine, Korea University, Seoul, Korea
Background: The CDK4I(cyclin dependent kinase 4 inhibitor) gene is on the chromosome 9p21. It encodes p16, which binds to CDK4, and inhibits phosphorylation of retinoblastoma protein(pRb) by D-type cyclin-CDK4 complex. D-type cyclin-CDK4 complex phosphorylates pRb which regulates transition of G1 to S phase of the cell cycle. So inactivation of the CDK4I gene leads to the dysregulation of the cell cycle and may contribute to the malignant progression of cells. Homozygous deletion of CDK4I gene was frequently found in human hematologic malignancies. The purpose of this study is to find the relationship between the CDK4I gene homozygous deletion and diverse acute leukemia.
Methods: We analyzed homozygous deletions of the CDK4I gene from 21 cases of acute leukemia by means of Southern blot analysis(10 B-cell acute Iymphocytic leukemias, 6 T-cell acute Iymphocytic leukemias, 5 acute myelogenous leukemias). Hybridization of EcoRI digested DNA using CDK4I probes(exon 1 and exon 2) obtained by PCR of human control DNA was performed.
Results:
1) We observed 4 cases(19%) of homozygous deletions in 21 cases of acute leukemia. 2) ALL 4 cases of homozygous CDK4I deletion were T-cell ALL which
accounted for 66%(4/6 cases) of T-cell ALLs. 3) Homozygous CDK4I deletions were not found in any cases of B-ALLs(0/10 cases) and AML(0/5 cases). 4) In 4 cases of homozygous deletion consistent results were obtained by 2 different CDK4I probes (pv 336-bp probe, pv 142-bp probe)
Conclusion: The high frequency of CDK4I homozygous deletions in T-ALLs supports that the inactivation of these genes plays an important role in the pathogenesis of
T-ALL.
Keywords: CDK4I, p16, Acute leukemia, Southern blot analysis,