Prognostic significance of serum progranulin level in de novo adult acute lymphoblastic leukemia patients.

Increased expression of progranulin (PGRN) has been reported in some hematological cancers, but limited information regarding its significance in acute lymphoblastic leukemia (ALL) is available. This study involved 60 subjects (40 de novo adult ALL patients and 20 controls). Serum PGRN level was measured by enzyme-linked immunosorbent assay and was correlated with patient outcome. Serum PGRN level was significantly higher in patients than controls. Serum PGRN level did not correlate with age, total leukocytic count, hemoglobin, platelets, absolute blast count in peripheral blood, lactate dehydrogenase, percent of blasts in bone marrow, gender, comorbidities, the presence of central nervous system infiltration, ALL phenotype, cytogenetics and risk of the disease. High serum PGRN level was not associated with inferior overall survival (OS) on univariate analysis. Regarding cumulative incidence of relapse (CIR) and disease-free survival (DFS), high PGRN level was associated with poor results on univariate analysis. Moreover, it tended to be independent risk factor on multivariate analysis for CIR but was not an independent predictor of inferior DFS. Serum PGRN level is significantly elevated in de novo adult ALL patients and may be used as a predictor of increased relapse risk.

Expression of thioredoxin-1 (TXN) and its relation with oxidative DNA damage and treatment outcome in adult AML and ALL: A comparative study.

OBJECTIVE: Thioredoxin-1 (TXN) is a key element in the elimination of reactive oxygen species as well as activation of tumor suppressor genes and DNA repair enzymes. Several studies showed that TXN was over expressed in solid tumors and this was correlated to poorer prognosis. However, TXN expression has been insufficiently studied, particularly in newly diagnosed adult acute leukemia. METHODS: This study was designed to evaluate the gene expression of TXN in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) adult patients and to investigate its association with oxidative DNA damage. The expression of TXN was analyzed using quantitative reverse transcriptase-polymerase chain reaction while oxidative DNA damage was evaluated by measuring serum 8-hydroxy-2-deoxyguanosine (8-OHdG) by enzyme-linked immunosorbent assay and strand breaks by the comet assay. RESULTS: We found that TXN was under expressed in both AML and ALL groups (P < 0.001 for both) as compared to the control group. Also TXN expression level was negatively correlated with serum 8-OHdG and tail moment in both AML (P = 0.042 and 0.047, respectively) and ALL (P < 0.001 and P = 0.02, respectively) while it showed no correlation with treatment outcome in either groups. DISCUSSION: This study suggests that TXN expression is hindered in adult acute leukemia which augments oxidative DNA damage and hence mutagenesis. CONCLUSION: This study provides a new insight into the pathogenesis of acute leukemia and suggests TXN as a new screening test for the risk for acute leukemia.

Beclin-1 and hypoxia-inducible factor-1α genes expression: Potential biomarkers in acute leukemia patients.

BACKGROUND: Beclin-1, an important autophagic gene, and hypoxia-inducible factor-1α (HIF-1α), the master regulator of the hypoxic response, are reported in several human cancers. However, their expressions in acute leukemia haven't yet been well investigated. OBJECTIVE: This study was designed to investigate the gene expression of beclin-1, microtubule-associated protein-1 light chain-3B (MAB1LC3B), the anti-apoptotic marker Bcl-2, and HIF-1α, as well as to evaluate the relationship between their expressions profile and prognosis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) adult patients. METHODS: The study involved 30 AML patients, 25 ALL patients, and 20 controls. Gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS: In both AML and ALL groups, beclin-1 and MAB1LC3B expressions were significantly down-regulated (p < 0.001), while HIF-1α (p < 0.01) and Bcl-2 (p < 0.001) expressions were significantly up-regulated compared to the control group. HIF-1α fold expression was significantly negatively correlated with beclin-1 (p < 0.01). Moreover, decreased beclin-1 gene expression and increased HIF-1α gene expression were both associated with poor survival, supporting their pivotal role in the development and progression of acute leukemia. CONCLUSIONS: Both Beclin-1 and HIF-1α could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia.

Expression of inhibitor of apoptosis protein (IAP) livin/BIRC7 in acute leukemia in adults: correlation with prognostic factors and outcome.

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.

High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma.

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin's lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg(-1) day(-1) for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 +/- 13.3% versus 58.9 +/- 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite 'group II', denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.

The impact of high-dose sodium selenite therapy on Bcl-2 expression in adult non-Hodgkin's lymphoma patients: correlation with response and survival.

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the expression of Bcl-2 in patients with non-Hodgkin's lymphoma (NHL). Fifty patients with newly diagnosed NHL were randomly divided into two groups. Group A-I received standard chemotherapy whereas group A-II received adjuvant sodium selenite 0.2 mg kg-1 day-1 for 30 days in addition to chemotherapy. Enzyme-linked immunosorbent assay was used to assess Bcl-2 at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant decline of Bcl-2 level after therapy in group A-II (8.6 +/- 6.9 ng/ml vs 3 6.9 +/- 7.9 ng/ml, P < 0.05). Also, complete response reached 60% in group A-II compared to 40% in group A-I. Significant increase in CD4/CD8 ratio was noticed in group A-II compared to group A-I after therapy (1.45 +/- 0.36 vs 1.10 +/- 0.28 p 0.04). Overall survival time in months was significantly longer in complete remission patients in group A-II (21.87 +/- 1.41) compared to group A-I (19.70 +/- 1.95) (p = 0.01). It is concluded that sodium selenite administration at the dosage and duration chosen acts as a down regulator of Bcl-2 and improves clinical outcome.

Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients.

The present study was undertaken to explore the effect of the administration of high doses of sodium selenite on apoptosis in polymorphonuclear leukocytes in patients with non-Hodgkin's lymphoma. Thirty patients with newly diagnosed non-Hodgkin's lymphoma were randomly divided into two groups. Group I was treated with chemotherapy and group II received 0.2 mg/kg/d sodium selenite in addition to chemotherapy. Flow cytometry was used for the monitoring of apoptosis on peripheral blood neutrophils at the time of diagnosis and after treatment in both groups of patients. Sodium selenite administration resulted in a significant reduction in neutrophils apoptosis (82+/-10% vs 32+/-18%, p<0.05) and this was associated with significant reduction in infection rate following chemotherapy (67% vs 20%, p<0.05). Also, significant improvement in cardiac ejection fraction was observed (62+/-4% vs 69+/-5% p<0.05). It is concluded that sodium selenite administration at the dosage chosen acts as a cytoprotective agent, alleviating side effects and immunosuppressive effects of cytotoxic chemotherapeutic agents.