Homozygous Deletion of CDK4I in Acute Leukemia.
- Author:
Jueng Ah KWON
1
;
Kap No LEE
Author Information
1. Department of Clinical Pathology, Seoul Red Cross Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
CDK4I;
p16;
Acute leukemia;
Southern blot analysis
- MeSH:
B-Lymphocytes;
Blotting, Southern;
Cell Cycle;
DNA;
Exons;
Hematologic Neoplasms;
Humans;
Leukemia*;
Phosphorylation;
Phosphotransferases;
Polymerase Chain Reaction;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma;
Retinoblastoma Protein;
S Phase;
T-Lymphocytes
- From:Korean Journal of Hematology
1998;33(3):322-333
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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 lymphocytic leukemias, 6 T-cell acute lymphocytic 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.
