Acute myeloid leukemia (AML) is a highly lethal hematological malignancy in adults and children. Abnormal proliferation of leukemia stem cells (LSC) with CD34+ and CD38- phenotypes are the main clinical features of AML. Patients with AML face drug resistance and treatment failure due to a default in stem and progenitor cells. Therefore, defining LSC properties is necessary for targeting leukemia-initiating cells. Mitochondrial mass and activity increase in AML initiating cells compared with normal stem cells. This idea has offered the inhibition of the mitochondrial translation machinery to reduce the number of leukemia-initiating cells in patients with AML Tigecycline is an FDA-approved microbial antibiotic that inhibits oxidative phosphorylation in mitochondria, resulting in the suppression of leukemia cell proliferation with little toxicity to normal cells. Thus, the present study was conducted to evaluate whether LSC is influenced by mitochondrial inhibition. We measured the IC50 of tigecycline in KG-1a AML cell lines. KG-1a AML cell lines were separated into CD34+ and CD34- cells by MACS. In the following, these cells were treated with 20 µM (IC50) tigecycline. The expression of Annexin/PI, Caspase 3, apoptotic genes (BCL2, BCLX, BAX, BAD, and P53) and proteins (P53, BAX, BCL2 and Caspase 9) was evaluated in CD34+ , CD34- and KG-1a AML cells. In addition, the telomere length and expression of hTERT were evaluated in this study. The results indicated that BCl2 (gene and protein) and BCLX gene dramatically decreased. In addition, BAD, BAX, and P53 gene and protein expression significantly increased in CD34+ AML cells compared to CD34- AML cells. The results also suggested that tigecycline induced intrinsic (Cleaved-caspase 9/Pro-Caspase 9 ratio) and p53-mediated apoptosis. Furthermore, hTERT gene expression and telomere length decreased in the tigecycline-treated groups. Taken together, our findings indicate that inhibition of mitochondrial activity with tigecycline can induce apoptosis in cancer stem cells and can be used as a novel method for cancer therapy.

Livin, a member of the inhibitor of apoptosis proteins has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of livin expression in childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to assess the expression of livin on leukemic blasts of de novo childhood ALL and its relevance to clinical and hematological findings, and treatment outcome. The expression of livin was analyzed in 80 patients with newly diagnosed childhood ALL using quantitative reverse transcriptase-polymerase chain reaction. The results of the study revealed that the expression levels of livin were higher in patients with favorable prognostic factors. Furthermore, livin expression was associated with a favorable early response to chemotherapy (leukemic blast <25% day 7 bone marrow response) (P = 0.001). Patients with high livin expression were associated with significantly higher CR rate (P = 0.02) and lower mortality rate (P = 0.05) than those with low livin expression. Kaplan-Meier curves demonstrated that high livin expression was associated with significantly longer DFS (P = 0.004) and overall survival (P = 0.02). Multivariate analysis demonstrated that livin expression was independent favorable prognostic factor for OS and DFS (P = 0.05 and P = 0.01, respectively). This study suggests that livin expression could be a novel prognostic marker in childhood ALL thus it could be incorporated into patient stratification and treatment protocols.

The clinical relevance of livin/BIRC7 expression is still controversial in different types of malignancies, therefore this study was designed to evaluate the gene expression of livin in Egyptian adult AML and ALL. Livin expression level was higher in patients with unfavorable prognostic factors at diagnosis in both ALL (p=0.002) and AML (p=0.042) and its level was negatively correlated with event free survival (EFS) and overall survival (OS) in both ALL (p<0.001for both) and AML (p=0.001 and 0.023 respectively). This study suggests that livin expression is a novel prognostic marker in adult acute leukemia and thus needs to be incorporated into the patient stratification and treatment protocols.

Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that conventional methods are seriously in error when assessing the risk of childhood leukaemia from exposure to man-made radionuclides released from nuclear installations.

The objective of this study was to describe trends in the incidence rates of primary lung cancer in a geographically defined Chinese population. Primary lung cancer cases (N=40,022) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-specific and age-adjusted incidence rates to the world standard population were examined in both males and females. Age-period-cohort (APC) model and Poisson regression were used to assess the cohort effects and incidence trends. Crude and age-adjusted incidence rates in the study period were: 66.2/100,000 and 45.2/100,000 in males; and 47.7/100,000 and 28.2/100,000 in females, respectively. The major birth cohort effect can be described as for those born before 1940, in every age group lung cancer incidence rate increased as the birth years advanced. For those born after 1940, age specific incidence rates decreased as the birth years advanced. Results from the Poisson regression analyses suggested a statistically significant increasing trend of incidence rates of lung cancer from 1981 to 1990 and changed little afterwards. Through first 10 years of the study period between 1981 and 2000, lung cancer incidence rates increased in both males and females. While the study results suggest that the age-adjusted incidence rates may have reached their peak and may even decline, as the Chinese population ages, and smoking prevalence remains high, the number of new lung cancer cases will continue to increase and overall burden of lung cancer will remain high.