[Expression of cyclin-dependent kinase inhibitors in leukemia]. 2003

J Polák, and S Peková, and J Schwarz, and T Kozák, and C Haskovec
Ustav hematologie a krevní transfuze, Praha. japol@uhkt.cz

BACKGROUND Leukemias develop due to defects in proliferation, differentiation and apoptosis, which take place in stem cells or progenitors of hematopoiesis. These processes have several crossing points, one of them is the role of inhibitors of cyclin-dependent kinases. The aim of this study was to study the expression of cyclin-dependent kinases inhibitors p21 Cip and p27 Kip and expression of proliferative antigen Ki-67 in leukocytes of human leukemia. RESULTS The expression of cyclin-dependent kinases inhibitors was detected at mRNA level mainly by comparative reverse-transcription polymerase chain reaction and in selected samples also by the real-time polymerase chain reaction. While p27 Kip expression in leukocytes of leukemic patients and healthy persons was universal, large differences in expression of p21 Cip were found both among individual patients of the same type of leukemia and between different types of leukemias and healthy persons. The p21 Cip expression was significantly higher in acute leukemias than in chronic ones and healthy persons. A comparison of p21 Cip expression with the clinical outcome of the leukemic patients showed that the group of 14 acute leukemia patients surviving more than 30 months had a significantly lower expression of p21 Cip than 12 patients of this type of leukemia who died within this time limit. Moreover, the results obtained on a smaller set of acute promyelocytic leukemia patients indicated that the lower p21 expression is connected with a better prognosis. CONCLUSIONS Our results pointed out the importance of the cyclin-dependent kinase inhibitor p21 Cip in human leukemias and indicated that the lower p21 Cip expression might be a positive prognostic factor in acute myeloid leukemia patients.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D016213 Cyclins A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators. Cyclin
D050759 Cyclin-Dependent Kinase Inhibitor p21 A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3. CDK2-Associated Protein 20 kDa,CDKN1 Protein,CDKN1A Protein,Cdk-Interacting Protein 1,Cdk2 Inhibitor Protein,Cell Cycle Regulator p21,Cyclin Kinase Inhibitor p21,Cyclin-Dependent Kinase Inhibitor 1A Protein,Senescent Cell-Derived Inhibitor Protein 1,p21 Cell Cycle Regulator,p21 Cyclin Kinase Inhibitor,CDK2 Associated Protein 20 kDa,Cdk Interacting Protein 1,Cyclin Dependent Kinase Inhibitor 1A Protein,Cyclin Dependent Kinase Inhibitor p21,Senescent Cell Derived Inhibitor Protein 1
D050760 Cyclin-Dependent Kinase Inhibitor p27 A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2. CDK Inhibitor p27,CDKN1B Protein,CDKN4 Protein,Cyclin-Dependent Kinase Inhibitor 1B,p27 CDK Inhibitor,p27 Kip1 Protein,p27Kip1 Protein,CDK Inhibitor, p27,Cyclin Dependent Kinase Inhibitor 1B,Cyclin Dependent Kinase Inhibitor p27,Kip1 Protein, p27,p27, CDK Inhibitor
D018797 Cell Cycle Proteins Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. Cell Division Cycle Proteins,Cell-Cycle Regulatory Proteins,cdc Proteins,Cell Cycle Regulatory Proteins
D018844 Cyclin-Dependent Kinases Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. Cyclin-Dependent Kinase,Cyclin-Dependent Protein Kinase,cdk Proteins,Cyclin-Dependent Protein Kinases,Cyclin Dependent Kinase,Cyclin Dependent Kinases,Cyclin Dependent Protein Kinase,Cyclin Dependent Protein Kinases,Kinase, Cyclin-Dependent,Kinase, Cyclin-Dependent Protein,Protein Kinase, Cyclin-Dependent

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