High expression of LMO2 predicts a favorable outcome in adult patients with BCR/ABL negative B-cell acute lymphoblastic leukemia.

The LIM domain only protein 2 (LMO2) is a key regulator of hematopoietic stem cell development. Expression of LMO2 has been evaluated in B-cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia; however, information concerning its role in breakpoint cluster region/Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) negative B-cell acute lymphoblastic leukemia (B-ALL) remains limited. The present study investigated LMO2 expression using quantitative polymerase chain reaction in 85 adult patients with BCR/ABL negative B-ALL, and associated the expression of LMO2 with established prognostic factors. LMO2 expression levels in patients with BCR/ABL negative B-ALL was not significantly different compared with control individuals (P=0.25). However, LMO2 expression levels were associated with the immunophenotypical features of the patients; a high LMO2 expression was associated with a higher incidence of complete remission (P=0.03) and lower rate of relapse (P=0.01), and patients with a high LMO2 expression had a significantly improved overall survival rate (P=0.01) and disease-free survival (P=0.01). The present results suggest that LMO2 expression is a favorable prognostic marker in adult patients with BCR/ABL negative B-ALL and may be used as a diagnostic marker and therapeutic target. However, additional studies regarding its prognostic role in patients with BCR/ABL negative B-ALL are required.

Prognostic Significance of Secreted Frizzled-Related Protein 2 Expression in Cytogenetically Normal Primary Acute Myeloid Leukemia.

BACKGROUND: Deregulation of secreted frizzled-related protein 2 (sFRP2) has been found in many types of cancer. However, the pattern of sFRP2 expression in acute myeloid leukemia (AML) is still unclear. METHODS: This study aimed to validate the prognostic significance of sFRP2 expression in 54 older patients with cytogenetic normal acute myeloid leukemia (CN-AML) using real-time quantitative polymerase chain reaction. RESULTS: sFRP2 expression was decreased markedly in patients compared with controls (P < 0.001). No correlation was found between sFRP2 gene expression and WBCs, hemoglobin, platelets, FAB type, NMP1 and FLT3/ITD mutations at diagnosis. All patients were treated with standard induction chemotherapy. Patients with high sFRP2 expression had higher incidence of complete remission rate (P = 0.04) and better overall survival (P = 0.026). Multivariate analysis revealed that high sFRP2 expression was a prognostic factor for older patients with CN-AML. CONCLUSIONS: This study demonstrated that sFRP2 gene expression at diagnosis had an impact on outcome of elderly CN-AML patients.

Prognostic significance of lymphoid enhancer-binding factor-1 expression in egyptian adult B-acute lymphocytic leukemia patients.

OBJECTIVE: Lymphoid enhancer-binding factor-1 (LEF-1) is a key transcription factor of wingless-type (Wnt) signaling in various tumors and it is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF-1 in acute lymphoblastic leukemia (ALL) and determined its specific prognostic significance in this disease. MATERIALS AND METHODS: We studied LEF-1 expression in 56 newly diagnosed B-acute ALL adult patients using real-time quantitative polymerase chain reaction to investigate whether LEF-1 expression was associated with clinical patient characteristics and treatment outcomes. RESULTS: High LEF-1 expression was associated with significantly poorer disease-free survival (p=0.03) and overall survival (p=0.005). Patients with high LEF-1 expression had a significantly higher relapse rate compared with low LEF-1 expression (p=0.01). CONCLUSION: We provide evidence that high LEF-1 expression is a prognostic marker in adult B-acute ALL patients.

Influence of interleukin-15 polymorphism on the survival of adult patients with acute lymphoblastic leukemia in Egypt.

The aim of this study was to analyze the association of the rs10519612 and rs17007695 polymorphisms with the risk of acute lymphoblastic leukemia (ALL) and also to evaluate their impact on the survival of adult patients with ALL. The study included 164 adult patients with ALL and 158 healthy subjects as a control group who were genotyped for the interleukin-15 (IL-15) gene using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We observed a higher risk of developing ALL for rs10519612 CC, rs17007695 TC and rs17007695 CC genotype carriers. There was increased risk for T-cell type in patients with the rs10519612 CC genotype. Notably, increased risk to develop B-cell type was found with rs17007695 TC and CC genotypes. There was no impact on overall survival or disease-free survival at 3 years. It is concluded that there is an association between both gene polymorphisms and the risk of ALL and with disease immunophenotype. However, there was no impact on the outcome of patients.

High expression of GTPase regulator associated with the focal adhesion kinase (GRAF) is a favorable prognostic factor in acute myeloid leukemia.

BACKGROUND: GRAF is a recognized tumor suppressor gene that was found inactivated in AML. However, the prognostic role of a GRAF transcript has not been studied in patients with AML. METHODS: In this study, we investigated the expression of the GRAF transcript by real time quantitative PCR in 60 AML patients and 30 healthy age and sex matched controls. RESULTS: GRAF expression was significantly lower in patients with AML when compared to controls (P=0.008). There were no significant differences in clinical features, FAB subtypes and cytogenetic risk subgroups between patients with high and low GRAF expression levels. Kaplan-Meier analysis showed that patients with high GRAF expression had longer overall survival (OS). Multivariate analysis revealed that, besides WBC count, GRAF expression was also an independent prognostic factor for AML. CONCLUSION: We provide evidence that high GRAF expression is a favorable prognostic marker in patients with AML.

MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR=2.513, 95% CI: 0.722-4.086, P=0.025). No such association was shown for heterozygous 677CT (OR=1.010, 95% CI: 0.460-2.218, P=0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR=1.1816, 95% CI: 0.952-3.573, P=0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR=1.046, 95% CI: 0.740-1.759, P=0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR=1.849, 95% CI: 0.935-2.540, P=0.024; OR=1.915, 95% CI: 1.202-3.845, P=0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P=0.001, P=0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy.

Prognostic value of plasma levels of thrombomodulin and von Willebrand factor in Egyptian children with acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia is the most common childhood malignancies, representing nearly one-third of all pediatric cancers. Thrombomodulin is a membrane glycoprotein in the vascular endothelium. Its plasma level depends on the integrity of the endothelium. Soluble thrombomodulin is derived from injured endothelial cells or proteolytically cleaved from thrombomodulin by proteases. Von Willebrand factor is a blood glycoprotein involved in homeostasis. Its plasma level increases in neoplastic diseases and arises from adverse changes in the endothelium. Severe endothelial dysfunction is present during the acute phase of acute lymphoblastic leukemia. Plasma levels of von Willebrand factor and soluble thrombomodulin have been used as indexes of endothelial dysfunction. OBJECTIVE: The aim of this study was to assess serum soluble thrombomodulin and von Willebrand factor levels in children with acute lymphoblastic leukemia during acute phase of the disease to assess their potential prognostic value. PATIENTS AND METHODS: Forty patients with acute lymphoblastic leukemia included 26 males and 14 females with their ages ranged from 2 to 10 years and 20 healthy children of matched age and sex were included in this study. We analyzed serum soluble thrombomodulin and von Willebrand factor levels by enzyme-linked immunosorbent assay. RESULTS: In children with acute lymphoblastic leukemia, there was a significant increase in soluble thrombomodulin, and von Willebrand factor levels during the acute phase of the disease. Children with an unfavorable outcome had higher levels of thrombomodulin and von Willebrand factor levels. CONCLUSIONS: Serum thrombomodulin and von Willebrand factor levels as a parameter of endothelial dysfunction during the acute phase of acute lymphoblastic leukemia might represent an additional prognostic marker in childhood acute lymphoblastic leukemia.

Frequency of red cell alloimmunization in patients with sickle cell anemia in an Egyptian referral hospital.

INTRODUCTION: Sickle cell anemia (SCA) is an important public health issue in Tanta, Egypt. Erythrocyte transfusions may reduce the morbidity of SCA, however, they are associated with numerous risks. Among other risk categories, alloimmunization to red cell antigens may result from transfusions. The objective of this study was to explore the frequency of red cell alloantibodies among SCA patients who received regular transfusions. MATERIALS AND METHODS: A total of 42 patients with SCA were included in this study. This work planned to study the presence of alloantibodies to different red cell antigens in multi-transfused SCA patients using the ID card micro-typing system. Clinical and laboratory data were collected and analyzed to find out the frequency, pattern and factors influencing red cell alloimmunization secondary to multiple blood transfusion in these patients. RESULTS: Of a total of 42 SCA patients included in the study, 21.4% of patients developed alloantibodies. The most common alloantibodies were anti-K, anti-E and anti-C. The rate of incidence of these alloantibodies was 7.1%, 4.8% and 4.8%, respectively. There was significant association between alloantibody and the rate of transfused blood. The mean age of patients with and without alloimmunization was 12.0 and 6.2 years. CONCLUSIONS: Alloimmunization to minor erythrocyte antigens of variable clinical significance is a frequent finding in transfused SCA patients. Regular screening for red cell alloantibodies would provide better management of these patients.

Prognostic Significance of NRAS Gene Mutations in Children with Acute Myelogenous Leukemia.

BACKGROUND: NRAS mutations are the most commonly detected molecular abnormalities in hematologic malignancies, especially in those of myeloid origin. OBJECTIVE: We aimed to determine the frequency of NRAS (NRAS(mutant)) mutation; and its prognostic significance in Egyptian children with acute myelogenous leukemia (AML). SUBJECT AND METHODS: Peripheral blood and bone marrow (BM) samples were taken from 39 de novo pediatric AML patients. Twenty subjects with matched age and sex were selected as a control group. Samples from patients and control were analyzed for Exons 1, 2 of NRAS gene using genomic PCR-SSCP method. RESULTS: NRAS mutations at the time of diagnosis was found in 6/39 (15.4%) AML cases. Patients with NRAS(mutant) had no significant improved clinical outcome than patients without mutation. Patients with NRAS(mutant) had similar complete remission (CR) rates compared with non-mutated patients (66.7% vs. 69.5%, P=0.43). Those in CR had a similar relapse rate regardless of the presence of NRAS(mutant) (RR 33.4% vs. 30.2%, P=0.26). However, an adverse prognosis for 3 year overall survival (OS) was associated with the presence of NRAS mutations. This adverse prognosis associated with NRAS mutations was also observed in terms of disease-free survival (DFS) (P=0.007). Univariate analysis showed that unfavorable prognostic factors for DFS were cytogenetic data (P = 0.005) and the NRAS gene mutation (P = 0.002). CONCLUSION: NRAS(mutant) did not contribute to increase the disease recurrence, however NRAS(mutant) was found to be a poor prognostic factor for children with AML. Further studies to confirm these findings are required because of the small number of patients with NRAS mutation.

Prognostic significance of FLT3 internal tandem duplication in egyptian patients with acute myeloid leukemia with normal or favorable risk cytogenetics.

Internal tandem duplication (ITD) of the FLT3 gene (FLT3/ITD) has been linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate. The aim of this study was to evaluate the prognostic significance of FLT3/ITD in patients with de novo AML and normal or favorable risk cytogenetics (NFC-AML). Blood samples from 39 patients with AML were subjected to PCR of exons 14 and 15 of the FLT3 gene. Patients included 25 with normal cytogenetics, 8 with t(15;17), 4 with t(8;21) and 2 with inv(16). FLT3/1ITD was found in 6/39 (15.4%) patients, 4 of them showed normal cytogenetic, 1 positive for t(15;17) and 1 positive for t(8;21). Patients were M1 3/13, M2 2/12, M3 1/9, M4 0/4 and M5 0/1. The patients were followed up for a mean of 34.5 +/- 2.3 months. The complete remission (CR) rates for the FLT3/ITD+ and FLTITD- groups were 50% vs 63.6%, while the relapse rates were 50% vs 28.6% respectively. Interestingly, disease free survival (DFS) at 3 years was significantly different in studied patients: DFS was 5% in patients with FLT3/ITD+ vs 30% of patients with FLT3/ITD- (P = 0.001). Our data suggest a possible high prognostic value of FLT3/ITD in patients with normal/favorable cytogenetics.

Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients.

BACKGROUND: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. OBJECTIVES: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. MATERIALS AND METHODS: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 +/- 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. RESULTS: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. CONCLUSIONS: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection.