Expression of cell cycle regulatory genes in chronic myelogenous leukemia.
OBJECTIVE
Cell cycle regulatory genes are frequently altered in a variety of malignancies. The structure and pattern of expression of eight genes involved in cell division cycle control were studied in leukemic cell samples prepared from bone marrow of patients affected by chronic myelogenous leukemia.


METHODS
Ten cell preparations were obtained from patients in the chronic phase, five from those in myeloid blast crisis and five from those in the lymphoid acute phase. Moreover, bone marrow CD34+ cells, purified from healthy subjects and patients with chronic myelogenous leukemia (both during chronic and acute phases), were analyzed. The investigated genes were RB1, p53 and six cyclin-dependent kinase inhibitor genes (p15INK4B, p16INK4A, p18INK4C, p21WAF1/CIP1, p27Kip1, p57Kip2).


RESULTS
We found that none of these genes is structurally altered in either the chronic or acute phases, with the single exception of the p16INK4A gene, which was homozygously deleted in 1 case of lymphoid evolution. p57Kip2 expression is down-regulated during the evolution towards the blast crisis both in malignant and CD34+ cells. In addition, a significant up-regulation of p15INK4B gene expression is observable during the development of the acute phase of malignancy.


CONCLUSIONS
The transcriptional modulation of some cyclin-dependent kinase inhibitors might contribute to the fatal blast crisis of chronic myelogenous leukemia.
Iolascon
A
A
Dipartimento di Biomedicina dell'Età Evolutiva, Università di Bari, Italy. iolascon@percom.it
Della Ragione
F
F
Giordani
L
L
Serra
A
A
Saglio
G
G
Faienza
M F
MF
D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D004791:Enzyme Inhibitors; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D016161:Genes, Retinoblastoma; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D020409:Molecular Motor Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; C493971:CDKN2C protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C075341:KIP2 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27