Prognostic value of CD25/CD123 pattern of expression in acute myeloid leukemia patients with normal cytogenetic.

This study was designed to assess the significance of interleukin-2 receptor (CD25) and inteleukin-3 receptor (CD123) expression in cytogenetically normal acute myeloid leukemia (CN-AML) patients. The current study includes 80 CN-AML (≤ 60 years) before the start of therapy. Blast cells expression for CD25 and CD123 were identified by flowcytometry in fresh bone marrow samples. CD25+/CD123-; CD25-/CD123+. CD25+/CD123+, CD25-/CD123- expression were as follow: 10/80 (12.5%); 18/80 (22.5%); 17/80; (21.25%), 35/80 (43.5%) respectively. The total CD25 expression was detected in 27/80 (33.75%), and CD123 expression was detected in 35/80 (43.75%%). CN-AML patients showed CD25+/CD123+ co-expression had the lowest induction remission rate and the shortest overall survival as compared to those lack co-expressions (P <0.01; P = 0.023 respectively). Also, there is strong positive association between CD25+/CD123+ co-expression and FLT3 mutations (P<0.001) and negative one with NPM1 mutation (P<0.001). In conclusion: CD25+/CD123+ co-expression in CN-AML patients define a subgroup of patients with adverse outcome. Identification of CD25/CD123 expression in CN-AML patents at diagnosis could be included in risk stratification. There is strong association between CD25+/CD123+ positive expression and FLT3 mutations.

Clinical value of CD25/CD123 co-expression in acute myeloid leukemia patients.

BACKGROUND: This study aimed to assess the significance of combined expression of interleukin-2 receptor (CD25) and the interleukin-3 receptor (CD123) in acute myeloid leukemia (AML) patients. METHODS: The expression of CD25 and CD123 on blast cells in bone marrow samples were identified by flowcytometry in 94 patients (⩽ 60 years old) with de novo acute myeloid leukemia (AML) treated at the Mansoura University Oncology Center (MUOC). RESULTS: Of the 94 samples at diagnosis there were 17 (18.1%) CD25+/CD123+ (double positive) cases; 25 (26.6%) CD25+/CD123- (single positive); 32 (34.0%) CD25-/CD123+ (single positive) cases; 20 (21.3%). CD25-/CD123- (double negative). Most of the AML patients have double CD25+/CD123+ were significantly associated with poor and intermediate risk as compared to those associated with those in the good risk group (P= 0.005). The lowest induction of remission was recorded in AML patients have double CD25+/CD123+ expression as compared to the remaining AML patient group. Study the effect of these biomarkers on the overall survival reveal that AML patients exhibited double CD25+/CD123+ expression had significantly shorter overall survival as compared to negative ones. CONCLUSION: Double CD25+/CD123+ co-expression in AML patients is a dismal prognostic marker and could be used as novel biomarker for risk stratification for AML patients.

Upregulation of CD200 is associated with regulatory T cell expansion and disease progression in multiple myeloma.

Immune dysfunction is an important feature of multiple myeloma (MM) leading to infections, enhancement of tumour growth and resistance to chemotherapy. The overexpression of CD200, expansion of T regulatory (Treg) cell and increased levels of immune modulatory cytokines like IL10, IL6 and transforming growth factor beta (TGFß) were suggested to have a role in this context. The aim of this study was to assess CD200 expression, Treg percentage by flow cytometry and immune modulatory cytokines (IL10, IL6, TGFß) by enzyme-linked immunosorbent assay in MM patients at diagnosis. This study included 50 MM patients at diagnosis and 20 healthy controls. The positive CD200 expression was detected in 72% of MM patients. Among the CD200 positive group, 4/13 patients (30.8%) were classified as stage I, 18/23 (78.3%) were in stage II and 14/14 (100%) were in stage III; according to International scoring system. Treg percentage was significantly higher in stage III, followed by stage II then stage I (p < 0.01). Serum IL6, IL10 and TGFß were significantly higher in MM patients as compared with controls (p < 0.01, p < 0.01, p < 0.05, respectively). The increased expression of CD200 and Treg percentages was associated with increased severity biomarkers (serum LDH and ß2 microglobulin). The degree of CD200 expression was significantly positively correlated to Treg percentage (r = 0.565, p < 0.01). Analysis of the CD200 negative patients had a better progression free survival (p = 0.032) and overall survival (p = 0.04) as compared with those positive for CD200 expression. These findings illustrate a clear correlation between myeloma cell CD200 expression level and the frequency of immunosuppressive Treg cells. In conclusion, increased expression of CD200, expansion of suppressive Treg cells and elevation of cytokines might have a role in MM progression in this cohort of patients. Copyright © 2015 John Wiley & Sons, Ltd.

Prognostic impact of serum 25-hydroxivitamin D [25(OH)D] concentrations in patients with lymphoid malignancies.

The incidence of lymphoid malignancies has been increasing rapidly. Despite growing evidence for a relationship between serum 25-hydroxivitamin D [25(OH)D] concentrations and solid tumor risk, far less is known about the relationship between 25(OH)D and the risk of hematologic malignancy. This study aimed to assess the prognostic relevance of serum 25(OH)D concentrations in patients with B chronic lymphocytic leukemia (B-CLL) and non Hodgkin's lymphoma (NHL). The study was carried out on 195 newly diagnosed patients (75 B-CLL and 120 NHL) as well as 30 normal healthy controls. For all patients and normal controls serum 25(OH)D concentrations were assayed by enzyme-linked immunosorbent assay. Serum 25(OH)D levels were significantly lower in B-CLL and NHL patients as compared with normal controls (P = 0.00 for both). Also, there are significant associations between serum 25(OH)D levels and positive CD 38, positive ZAP 70 as well as Binet stages (χ(2) = 16.071, 16.644, 21.134 respectively; P = 0.00 for all) in the B-CLL patient group. Moreover, there are significant associations between serum 25(OH)D status and international prognostic index (IPI), performance status (χ(2) = 6.994, 9.212, P = 0.02, 0.01 respectively), but not with clinical stages (χ(2) = 3.115, P = 0.539) in NHL. Multivariate analysis revealed that 25(OH)D insufficiency is an independent poor prognostic factor in both B-CLL and NHL patient groups. In conclusion, 25(OH)D insufficiency is an independent poor prognostic factor in patients with B-CLL and NHL. 25(OH)D might be a therapeutic target in lymphoid malignancies.

Neutrophil Apoptosis in Neutropenic Patients With Hepatitis C Infection: Role of Caspases 3, 10, and GM-CSF.

Patients with chronic HCV infection are prone to increased susceptibility bacterial infection due to neutropenia complicating the course of this disease. Neutropenia in those patients may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from 26 neutropenic patients with hepatitis C infection and nine age and sex-matched healthy control subjects were examined for the degree of apoptosis. Neutrophil apoptosis was quantified by flow cytometry through determination of annexin-V expression at 0 time (fresh neutrophil), and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic sera, with and without 10 µg GM-CSF. Caspases 3, 10 were assessed colormetrically in neutrophils at 0 times and after 24 h culture. At 0 time culture the neutrophil apoptosis of the HCV patients was in significantly higher as compared to that of normal control (P = 0.059). At 24 h culture patients neutrophils cultured with neutropenic patients own sera showed neutrophil apoptosis significantly increased as compared to that at 0 time culture and this effect was significantly attenuated in similar culture with addition of GM-CSF (P < 0.001). On the other hand patient's neutrophil cultured with normal sera showed insignificantly increased neutrophil apoptosis at 24 h culture as compared to that at 0 time culture. Caspases 3 and 10 activities were significantly higher in patients neutrophil after 24 h cultured with patients own sera as compared to 0 time culture (P < 0.001 for both). Addition of GM-CSF to the neutrophil culture down regulates the caspases 3 and 10 activities. The correlation study between annexin-V expression and caspases activities revealed a borderline positive correlation between annexin-V and caspase 3 (r = 0.376, P = 0.058), and significant positive correlation with caspase 10 activity (r = 0.494, P = 0.01). In conclusion, these findings suggest that enhanced neutrophil apoptosis demonstrated in neutropenic patients with HCV infection might be induced through activation of caspase 10 and is attenuated by GM-CSF.

Soluble angiopoietin-2/sTie2 receptor ratio is an independent prognostic marker in adult acute myeloid leukemia.

AIM: Angiogenesis is the formation of new blood vessels from preexisting one. The angiopoietins act a central role in these process. The aim of the present study is to the assess the impact of the circulating levels of angiopoietin-1 (Angi-1), Angiopoietin-2 (Angi-2), soluble Tie2 receptor (sTie2), and calculated Angi-2/sTie2 ratio on overall survival in 71 acute myeloid leukemia patients and 19 normal controls. MATERIALS AND METHODS: Ang-2, and calculated angi-2/sTie values were significantly higher in AML patients as compared to healthy volunteer (P= 0.002, 0.015 respectively) on the other hand Angi-1 was not significantly different in patients and control. RESULTS: In univariate Cox proportional hazards model Angi-2, sTie2, angi-2/sTie2 ratio were predictive of poor survival. In multivariate analysis the calculated angi-2/sTie2 ratio is independent prognostic factor, with relative risk of 3.939, with 95% confidence interval 0.002-0.001. CONCLUSION: The calculated angiopoietin-2/sTie2 ratio represent an independent prognostic factor in AML and its value should be considered when considering anti angiogenic therapy.