The Expression of P53, MDM2, c-myc, and P14ARF Genes in Newly Diagnosed Acute Lymphoblastic Leukemia Patients.

The treatment response of acute lymphoblastic leukemia (ALL) depends on the percentage of lymphoblasts, cytogenetic aberrations, and altered gene expression. The analysis of the gene expression is applicable for determination of risk stratification and prognosis of cancers. c-MYC, P14ARF, MDM2, and P53 play a vital role in cell survival through a functional network. This study aimed to investigate the expression of these genes, also their correlation with immunophenotypic subtypes of ALL and the percentage of blasts. Real-time PCR was performed for the expression analysis of P53, MDM2, c-MYC, and P14ARF in the bone marrow or peripheral blood samples of 52 ALL patients and 13 normal samples as controls. The morphological analysis and flow cytometry were carried out to examine the phenotypes and percentage of lymphoblasts. The decreased expression levels of P53 and MDM2 were seen in ALL patients compared with control group. In T cell subgroup of ALL the expression of P14ARF gene was more decreased among other subgroups. The expression of MDM2 was decreased in ALL patients who were under the age of 16. Based on our study, the interaction between P53 and MDM2 might be more complex and different from reports published in previous studies. Our findings showed that MDM2 is not negatively correlated with P53, at least in our samples. It can be very effective on the current and future studies to use different techniques for analysis of genome, transcriptome, and proteome in definitive risk stratification and prognosis determination.

Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-κB axis: Shedding new light on resistance to Aprepitant.

While a batch of efforts are fastened on synthesizing the novel targeted anti-cancer agents, recent investigations have achieved a breakthrough in identifying a favorable anti-tumor activity for some supportive drugs, which their safety have been confirmed thus far. The results of the present study highlighted the efficacy of Aprepitant, an oral antagonist of the neurokinin-1 receptor (NK1R), against both APL (NB4) and pre-B ALL (Nalm-6) cell lines; however, a differential sensitivity pattern was found in these cells. To the best of our knowledge, this is the first time that the molecular mechanisms of resistance to Aprepitant have been investigated and, herein, we proposed that the effectiveness of Aprepitant could be overshadowed, at least partially, through over-activated nuclear factor-κB in Nalm-6 pre-B ALL cells. In contrast to Nalm-6, the cytotoxic property of Aprepitant in NB4 was divulged at the lower concentrations. Of particular interest, we found that the cytotoxicity of the inhibitor became even more evident in the synergistic experiments, where an enhanced reduction in viability was noted after treatment of NB4 cells with ATO-plus-Aprepitant. The stimulatory effect of NK1R inhibition on ATO cytotoxicity is probably mediated through up-regulation of p73, which can subsequently engage p21 and NF-κB pathway via transcriptional suppression of c-Myc. Taken together, the present study suggests that inhibition of NK1R using Aprepitant, either alone or in combination with chemotherapeutic drugs, could be a novel therapeutic strategy for the treatment of acute leukemia, especially APL, that may be clinically accessible in the near future.

Status of blood transfusion in World Health Organization-Eastern Mediterranean Region (WHO-EMR): Successes and challenges.

BACKGROUND: Blood products are used for patient treatment and survival in the cases of major surgery, hematological disorders or cancer therapy. Presently the main blood components are not yet replaceable by artificial products and all activities related to blood transfusion is highly dependent on the healthcare development of each country. The World Health Organization Eastern Mediterranean Region (WHO-EMR) comprises of 21 member states with variable socio-economic status effective on blood transfusion activities. The fundamental motivation behind this research was to accumulate some data of blood practices in this region and to have an appropriate image of the WHO-EMR region. MATERIAL AND METHODS: The data were collected through the published papers or data, blood transfusion services websites, and the other health official websites like WHO. RESULTS: Among WHO-EMR countries there are some with a nationally organized blood transfusion establishment such as Egypt, Iran, Iraq, Kuwait, Morocco, Oman, Pakistan, and Syria. In a few, blood transfusion administrations are hospital-based like Saudi Arabia. The others are run by Red Crescent such as Bahrain, Tunisia and UEA or by Red Cross like Lebanon. Only Iran and UAE succeed to have 100% voluntary non-remunerated blood donors; however, most of them are still under the weight of family/replacement blood donation such as Afghanistan, Egypt, Iraq, Lebanon, Morocco, Saudi Arabia and Sudan or even paid donors like Pakistan and Yemen. The haemovigilance and training programs have been implemented in some countries including Bahrain, Iran, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Tunisia and UAE. Unfortunately, there are rare and inaccessible information about some EMR states like Djibouti, Palestine and Somalia so that little data can be independently discovered. CONCLUSION: In these countries different measures ought to be additionally designated to ensure blood products adequacy and safety such as the development of well-coordinated national blood transfusion centers with the increased government commitment, the establishment of a well-organized system for voluntary non-remunerated blood donor recruitment, the establishment of well-equipped laboratories for screening donor samples for transfusion transmitted infections (TTIs) for at least mandatory tests recommended by WHO, the implementation of an educational/training program for professionals working in the blood transfusion establishments or hospitals, the regular audit on the quality and the integrity of the blood transfusion chain, and the development of a regional network of collaboration to bolster the neighboring nations in the EMR through effective communication tools.