The Expression And Preliminary Functional Research Of Cyclin C In Childhood Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia(ALL) is one of the most common malignant tumors in children, and constitutes eighty percent of all childhood leukemia. However, we still know little about the molecular mechanisms underlying ALL pathogenesis. Previous studies suggested that both environmental and genetic factors contribute to the development of leukemia. Cellular transformation to malignancy is the result of the activation of oncogene or the deactivation of tumor suppressor genes(TSG), and the latter is the main mechanism of oncogenesis in many tissues. Therefore, To discover new TSGs mutated in leukemic cells and compensating their functions by introducing wild type copies provide a new strategy for leukemic gene therapy.Cytogenetic and molecular genetic analysis suggest that almost all tumour cells have nonrandom loss of chromosome segments,which may harbor a gene(s) involved in carcinogenesis. Many researches showed that the loss of heterozygosity(LOH) can be found in many chromosomes of childhood ALL, among them, chromosome band 6q is one of the most frequently deletion regions. There are several common deletion regions in ALL: 6q12-21, 6q14-21, 6q21, 6q21-22, 6q21-23, 6q23, 6q23-24, 6q23.1-27 and 6q25-27.6q21 is the most frequent minimal deletion regions, suggesting that this region might harbor a TSG. Furthermore, researches abroad detected high frequencies of allelic LOH at 6q21,defined by microsatellite marker D6S1709-D6S434. The protophasal study of our laboratory using even higher density of microsatellite site analysis showed that there is a common minimal deletion region defined by microsatellite marker D6S1709-D6S301 spanning 2cM, which strongly suggests that there may be an unidentified tumor suppressor gene(s) closely associated with childhood ALL located in this region.Cyclin C (CCNC) is a family member of cyclins , which locates on 6q21.The preliminary functional analysis of CCNC shows that it participates in the transition of G₁/S phase during the cell cycle. While others thought that it is the regulatory protein of G₀ phase. At the same time, it is closely associated with cell growth as one of the lalpha,25-dihydroxyvitamin D(3) responding gene. Some scholars examined the expression of CCNC in childhood ALL with 6q deletion and found that there is more than ninety percent allelic deletion of CCNC. Therefore, CCNC...