The prognostic potential of bone marrow cyclin E and P27, in Egyptian patients with acute myeloid leukemia.

Cyclin E and the cyclin dependent kinase inhibitor P27 are two important regulators of the G1-S transition modulating the activity of cyclin-dependent kinases. Aberrations in the cell cycle control are often observed in tumors and might even be mandatory in tumor development. There are few molecular biologic determinants that may be prognostic for patients with acute myeloid leukemia (AML). To investigate the importance of cell cycle defects in AML, the cellular levels of cyclin E and the cyclin-dependent kinase inhibitor P27 (Kip 1) were evaluated in thirty AML patients (11 males and 19 females) diagnosed by standard clinical, morphological and immunophenotypic criteria and staged according to the FAB classification. Using immunoblot analysis, cyclin E and P27 were detected in blast cells of AML patients who were then treated by the standard AML chemotherapeutic protocol and were followed up. With respect to cyclin E, it was detected in 9/30(30%) AML cases among them 13.3% (4/30 cases) exhibited very strong bands while 16.6% (5/30 cases) showed faint bands. Cyclin E was high among M4/M5 cases and low among M3 cases and showed a statistically significant positive correlation with percentage of blast cells, aberrant phenotype and abnormal karyotype at diagnosis. It also showed a significant negative correlation with complete remission (CR) rates. All our AML cases exhibited P27 at low and high levels as seen in 19/30 (63.4%) and 11/30 (36.6%) cases, respectively. P27 showed a statistically significant negative correlation to the percentage of blasts at diagnosis and a significant positive correlation with achievement of CR. A significant negative correlation between P27 and cyclin E (P < 0.004) was observed as well. The present study suggested that levels of cell cycle regulators cyclin E and P27 can be used as a useful prognostic molecular markers in AML patients.

Effect of surgically-induced weight loss on inflammatory mediators and peripheral blood monocyte CD11b expression in morbid obesity.

Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers. Expression and release of inflammation-related adipokines, generally, rise as adipose tissue expands. In the present study we evaluated the level of serum mediators concerned in inflammation and monocyte activation (TNF-alpha, hs-CRP, MCP-1) together with percentage of CD11-b expression on monocytes in a group of morbidly obese individuals (n = 20) before and (3-6 months) after restrictive surgery, and in 15 healthy normal weight individuals. Serum MCP-1, TNF-alpha and hs-CRP were assayed by enzymatic immunoassay, while the percentage of CD11b expression on monocytes was assayed by flow cytometry. The total lipid profile and random blood glucose levels were also assessed. Morbidly obese individuals ( before surgical weight loss) had significantly increased levels of MCP-1, TNF-alpha, hs-CRP, CD11b expression on monocytes as compared to controls (P < 0.01). Levels of MCP-1, TNF-alpha, hs-CRP were significantly decreased 3 to 6 months after restrictive surgery than before the operation (P < 0.01). hs-CRP, MCP-1 and TNF-alpha were positively correlated versus each other. TNF-alpha and hs-CRP also showed positive correlation with the body mass index. Our data suggested that the studied serum and monocyte parameters may link obesity with systemic inflammation and metabolic disorders. The interactions of MCP-1, CD11b and other inflammatory parameters might provide the basis for development of new therapies for this syndrome.