|
|
 Previous Article | Table of Contents | Next Article 
Homozygous loss of the cyclin-dependent kinase 4-inhibitor (p16) gene in
human leukemias
S Ogawa, N Hirano, N Sato, T Takahashi, A Hangaishi, K Tanaka, M Kurokawa, T Tanaka, K Mitani and Y Yazaki
Third Department of Internal Medicine, Faculty of Medicine, University of
Tokyo, Japan.
Recently, it has been shown that the homozygous deletion of the cyclin-
dependent kinase-4 inhibitor (CDK4I;p16) gene, which is mapped to
chromosome 9p21, is frequently observed in a wide spectrum of human
cancers, including leukemias. Therefore, the CDK4I gene is thought to be a
putative tumor-suppressor gene. We report here that both alleles of the
CDK4I gene were completely or partially deleted in human leukemia cells
derived from both patients and established cell lines. Thirty-seven
hematopoietic cell lines and samples from 72 patients with leukemias were
examined for homozygous loss of the CDK4I gene locus by Southern blot
analysis. We found that a part or the whole of the CDK4I gene was
homozygously deleted in 14 of the 37 (38%) cell lines and 4 of 72 (6%)
samples from leukemia patients, including 45 with acute myelocytic
leukemia, 14 with acute lymphocytic leukemia (ALL), and 13 with chronic
myelocytic leukemia in blastic crisis. In the cell lines, the homozygous
deletion of the CDK4I gene was detected in a variety of cell lineages,
whereas all 4 cases showing the homozygous deletion were confined to ALL.
It should be noted that 2 of them had no cytogenetic abnormalities of
chromosome 9. Our results suggest that loss of the CDK4I function may
contribute to immortalization of human leukemia cells and play a causative
role at least in development of human lymphocytic leukemias.
Volume 84,
Issue 8,
pp. 2431-2435,
10/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. K. Mukhopadhyay, E. Weisberg, D. Gilchrist, R. Bueno, D. J. Sugarbaker, and M. T. Jaklitsch
Effectiveness of Trichostatin A as a Potential Candidate for Anticancer Therapy in Non-Small-Cell Lung Cancer.
Ann. Thorac. Surg.,
March 1, 2006;
81(3):
1034 - 1042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Passioura, A. Dolnikov, S. Shen, and G. Symonds
N-Ras-Induced Growth Suppression of Myeloid Cells Is Mediated by IRF-1
Cancer Res.,
February 1, 2005;
65(3):
797 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Vaque, J. Navascues, Y. Shiio, M. Laiho, N. Ajenjo, I. Mauleon, D. Matallanas, P. Crespo, and J. Leon
Myc Antagonizes Ras-mediated Growth Arrest in Leukemia Cells through the Inhibition of the Ras-ERK-p21Cip1 Pathway
J. Biol. Chem.,
January 14, 2005;
280(2):
1112 - 1122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Jenab-Wolcott, D. Rodriguez-Correa, A. H. Reitmair, T. Mak, and N. Rosenberg
The Absence of Msh2 Alters Abelson Virus Pre-B-Cell Transformation by Influencing p53 Mutation
Mol. Cell. Biol.,
November 15, 2000;
20(22):
8373 - 8381.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Imai, M. Kurokawa, K. Izutsu, A. Hangaishi, K. Takeuchi, K. Maki, S. Ogawa, S. Chiba, K. Mitani, and H. Hirai
Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis
Blood,
November 1, 2000;
96(9):
3154 - 3160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mostecki, A. Halgren, A. Radfar, Z. Sachs, J. Ravitz, K. C. Thome, and N. Rosenberg
Loss of Heterozygosity at the Ink4a/Arf Locus Facilitates Abelson Virus Transformation of Pre-B Cells
J. Virol.,
October 15, 2000;
74(20):
9479 - 9487.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Faderl, H. M. Kantarjian, T. Manshouri, C.-Y. Chan, S. Pierce, K. J. Hays, J. Cortes, D. Thomas, Z. Estrov, and M. Albitar
The Prognostic Significance of p16INK4a/p14ARF and p15INK4b Deletions in Adult Acute Lymphoblastic Leukemia
Clin. Cancer Res.,
July 1, 1999;
5(7):
1855 - 1861.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Mulloy, T. Kislyakova, A. Cereseto, L. Casareto, A. LoMonico, J. Fullen, M. V. Lorenzi, A. Cara, C. Nicot, C.-Z. Giam, et al.
Human T-Cell Lymphotropic/Leukemia Virus Type 1 Tax Abrogates p53-Induced Cell Cycle Arrest and Apoptosis through Its CREB/ATF Functional Domain
J. Virol.,
November 1, 1998;
72(11):
8852 - 8860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Villuendas, M. Sanchez-Beato, J. C. Martinez, A. I. Saez, B. Martinez-Delgado, J. F. Garcia, M. S. Mateo, L. Sanchez-Verde, J. Benitez, P. Martinez, et al.
Loss of p16/INK4A Protein Expression in Non-Hodgkin's Lymphomas Is a Frequent Finding Associated with Tumor Progression
Am. J. Pathol.,
September 1, 1998;
153(3):
887 - 897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Arora and D. F. Jelinek
Differential Myeloma Cell Responsiveness to Interferon-alpha Correlates with Differential Induction of p19INK4d and Cyclin D2 Expression
J. Biol. Chem.,
May 8, 1998;
273(19):
11799 - 11805.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Urashima, J. A. DeCaprio, D. Chauhan, G. Teoh, A. Ogata, S. P. Treon, Y. Hoshi, and K. C. Anderson
p16INK4A Promotes Differentiation and Inhibits Apoptosis of JKB Acute Lymphoblastic Leukemia Cells
Blood,
November 15, 1997;
90(10):
4106 - 4115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. R. Kees, P. R. Burton, C. Lu, and D. L. Baker
Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome
Blood,
June 1, 1997;
89(11):
4161 - 4166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hangaishi, S. Ogawa, K. Mitani, N. Hosoya, S. Chiba, Y. Yazaki, and H. Hirai
Mutations and Loss of Expression of a Mismatch Repair Gene, hMLH1, in Leukemia and Lymphoma Cell Lines
Blood,
March 1, 1997;
89(5):
1740 - 1747.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pinyol, L. Hernandez, M. Cazorla, M. Balbin, P. Jares, P. L. Fernandez, E. Montserrat, A. Cardesa, C. Lopez-Otin, and E. Campo
Deletions and Loss of Expression of P16INK4a and P21Waf1 Genes Are Associated With Aggressive Variants of Mantle Cell Lymphomas
Blood,
January 1, 1997;
89(1):
272 - 280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D. Ragione, G. L. Russo, A. Oliva, C. Mercurio, S. Mastropietro, V. D. Pietra, and V. Zappia
Biochemical Characterization of p16INK4- and p18-containing Complexes in Human Cell Lines
J. Biol. Chem.,
July 5, 1996;
271(27):
15942 - 15949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Ausserlechner, P. Obexer, G. J. Wiegers, B. L. Hartmann, S. Geley, and R. Kofler
The Cell Cycle Inhibitor p16INK4A Sensitizes Lymphoblastic Leukemia Cells to Apoptosis by Physiologic Glucocorticoid Levels
J. Biol. Chem.,
March 30, 2001;
276(14):
10984 - 10989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
