• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1587-1590
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• 2015

Background: Chronic lymphoid leukemia (CLL) is the most frequent type of adult leukemia. The Rai and Binet staging systems have been well recognized as standards for assessing the treatment requirements and overall survival in CLL patients. However, there is a need to seek newer prognostic markers to identify stable or progressive forms of CLL that will facilitate risk-adapted treatment strategies. Currently a molecular biomarker ZAP-70 has attracted interest as providing prognostic information in CLL patients. Objective: To determine the frequency of ZAP-70 positivity in B-CLL patients at disease presentation. Materials and Methods: From January 2011 to September 2014, 89 patients were diagnosed to have chronic lymphoid leukemia. Complete blood count was done on an automated analyzer (Cell Dyne, Abott Architect, USA), while immunophenotyping was conducted for each patient to establish the diagnosis of the disease. ZAP-70 expression was evaluated by flow cytometry. Data were compiled and analyzed by SPSS version 21. Results: Out of the total of 89 B-CLL patients, 62 (69.7%) were male and 27 (30.3%) were females with a male to female ratio of 2:1. The mean age was $57.5{\pm}12.1years$. The frequency of ZAP-70 positivity in our B-CLL patients was found to be 13.5%. ZAP-70 positivity was significantly correlated with stage III disease and high absolute lymphocytic count (P<0.05). No correlation of ZAP-70 could be established with age and gender (p>0.05). Conclusions: The frequency of ZAP-70 in our patients appears low. It is approximately half that in international data. We would recommend to screen all the newly diagnosed patients with CLL for ZAP-70 protein expression for risk stratification, family counseling and to predict overall survival.

• Journal of Acupuncture Research
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• v.30 no.4
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• pp.95-105
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• 2013

Objectives : The objective of this study was to investigate the effects of Curcuma longa $L_{INNE}$ pharmacopuncture at $ST_{36}$ on Complete Freund's Adjuvant(CFA)-induced arthritis in rats. Materials and methods : Arthritis was induced by injecting CFA subcutaneously into the left knee joint and paw, and Curcuma longa $L_{INNE}$ pharmacopuncture(CLL-A. $0.0343{\mu}g/kg$; CLL-B. $0.171{\mu}g/kg$; CLL-C. $0.343{\mu}g/kg$) was injected at $ST_{36}$ each other day for 5 times beginning on day 10 after the CFA injection. Paw edema, withdrawal response, hematological, serological and histological observation were assessed. Results : In paw edema volume all 3 groups(CLL-A, CLL-B, CLL-C) showed significant decrease compared to the CFA control group. In withdrawal response to reaction time and withdrawal response to force all 3 groups(CLL-A, CLL-B, CLL-C) showed significant increase compared to the CFA control group. In serum AST, group CLL-C showed significant decrease compared to the CFA control group. In histological observations, in all 3 groups, more normal chondrocytes were observed compared to the CFA control group and safranin O stain showed high positive reaction in the cartilage tissue close to the bone tissue. Conclusions : The results suggest that Curcuma longa $L_{INNE}$ Pharmacopuncture at $ST_{36}$ has a suppressing inflammation effect on Freund's adjuvant arthritis in rats.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9885-9889
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• 2014

Background: Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) is an antitumor candidate in cancer therapy. This study focused on effects of TRAIL, as a proapototic ligand that causes apoptosis, in B-CELL chronic lymphocytic leukemia cells (B-CLL). Materials and Methods: A population of HEK 293 cells was transducted by lentivirus that these achieved ability for producing the TRAIL protein and then HEK 293 cells transducted were placed in the vicinity of CLL cells. After 24 hours of co-culture, apoptosis of CLL cells was assessed by annexin V staining. Results: The amount of Apoptosis was examined separately in four groups: 293 HEK TRAIL ($16.17{\pm}1.04%$); 293 HEK GFP ($2.7{\pm}0.57%$); WT 293 HEK ($2{\pm}2.6%$); and CLL cells ($0.01{\pm}0.01%$). Among the groups studied, the maximum amount of apoptosis was in the group that the vector encoding TRAIL was transducted. In this group, the mean level of soluble TRAIL in the culture medium was 253pg/ml; also flow cytometry analyzes showed that proapotosis in this group was $32.8{\pm}1.6%$, which was higher than the other groups. Conclusions: In this study, we have demonstrated that TNF secreted from HEK 293 cells are effective in death of CLL cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7987-7990
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• 2015

Chronic lymphocytic leukemia (CLL)is the most common leukemia in adults in Western countries but is relatively rare in Asia. Immune hemolytic anemia, Evan's syndrome, lymphadenopathy, organomegaly and B symptoms are the main complaints of patients in CLL. The present retrospective analysis evaluated a group of 109 patients with CLL over a 9-year period, studying correlations between sex, age and overall survival. The patients were hospitalized in the Clinic of Hematology and Oncology, Kermanshah, Iran, between 2006 and 2014. Data analysis for sex and age was performed using IBM SPSS19 and overall survival was plotted by Kaplan-Meier plot, Log-rank test in Graph Pad prism 5 Software for five-year periods. The mean age of diagnosis for CLL patients was 60.73 years, 59.6% male. Survival rate patients was 64% and mean overall survival was 38.5 months. In the Rai system, fourteen patients (12.8%) had stage III and twenty eight patients (25.7%) had stage IV. Most frequent clinical features in patients with CLL were lymphadenopathy (38.7%) and organomegaly (34%), respectively. There is not relationship between sex and age in patients but overall survival rate in females was higher than in males. In Asian countries, CLL is more in male and in age above 60 years. Complaints about lymphadenopathy and virus infection are prevalent.

• BMB Reports
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• v.28 no.4
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• pp.281-289
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• 1995

Homogeneous human deoxycytidine kinase was purified in one step from a variety of spontaneous human leukemic cells (T-ALL, B-ALL, B-CLL, AML, CML), and from cultured T-lymphoblast cells (MOLT-4) using the newly developed affinity medium, $dCp_4$-Sepharose. Starting with an ammonium sulfate fraction, purification was achieved in one step with the kinase being eluted from a column by the end product inhibitor, dCTP. The purified deoxycytidine kinase from T-ALL cells phosphorylated deoxyadenosine and deoxyguanosine, as well as deoxycytidine. The enzyme purified from T-ALL and B-CLL cells yielded one major band with a molecular weight of 52 kDa determined by SDS-polyacrylamide gel electrophoresis. AML and CML cells yielded one 52 kDa band and an extra band of 30 kDa molecular weight. On the other hand, B-ALL and MOLT-4 cells showed a low molecular weight band of 30 kDa only. However, the electrophoretic mobilities of enzymatic activity in 12% non-denaturing gels were identical for the dCyd kinase from all different kinds of leukemic cell lines, except that the B-ALL, B-CLL, and MOLT-4 cell preparations had an extra minor peak, all at the same position. dAdo and dCyd phosphorylating activities comigrated indicating that these activities are all associated with the same protein. Two new methods, a disk implantation method and a nitrocellulose powder method were used with a small amount of enzyme protein to raise polyclonal antibodies against dCyd kinase purified from T-ALL cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.793-796
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• 2015

Background: Chronic lymphoid leukemia (CLL) is not an uncommon hematological malignancy which primarily affects elderly individuals. It is more common in developed world than in developing countries. The rational of this study was to determine the clinico-hematological profile in Pakistan. Materials and Methods: In this prospective cross sectional study, sixty patients with CLL were enrolled from January 2011 to June 2013. Data were analyzed with SPSS version 21. Results: The mean age was $59.0{\pm}9.2years$ (range 40-82) and the male to female ratio was 2.1:1. Peak age group was 60-70 years (38.3%) and 18.3% were under 50 years old. Major complaints were weakness (51.7%), fever (18.3%) and abdominal discomfort (13.3%). Main clinical findings were splenomegaly (46.6%), lymphadenopathy (36.6%) and pallor (26.7%). Some 16.7% were diagnosed incidentally. The mean hemoglobin was $10.8{\pm}2.4g/dl$, with a total leukocyte count of $91.5{\pm}87.8{\times}10^9/l$ and platelets $197.8{\pm}103.2{\times}10^9/l$. Anemia and thrombocytopenia were seen in 26.7% and 21.7% of cases, respectively. High LDH and hyperuricemia were detected in 15% each and elevated serum creatinine was seen in 11.6%. According to Rai staging 11.6% were in stage 0, 13.3% stage 1, 26.7% each for stage II and stage III while 21.7% patients were in stage IV. Conclusions: CLL in our patients in Pakistan, unlike in the West, is seen in a relatively young population with male predominance. Primarily disease is of B-cell origin and about 2/3 of the patients present at advanced stage.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6007-6010
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• 2015

Background: Chronic lymphoid leukemia (CLL) is a malignant hematopoietic disorder, the most common of all adult leukemias with a distinctive immunophenotype. It is well established that CLL patients can have autoimmune complications, amongst them autoimmune hemolytic anemia as the most frequent. This study was carried out to determine the frequency of direct Coombs Test positivity in CLL patients and its possible correlation with Rai staging, hematological parameters and biochemical markers. Materials and Methods: This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty untreated patients with B- chronic lymphoid leukemia were enrolled. Complete blood count, direct Coombs test, serum urea, creatinine, uric acid and LDH levels were determined. Data were compiled and analyzed using SPSS version 21. Results: Out of 60 patients, 42(70%) were males and 18(30%) were females. Mean age was $59{\pm}9.2years$. Male to female ratio was 2.1: 1. The frequency of direct antiglobulin test (DAT) positivity was found to be 23.3%. The monospecific IgG was positive in 11 patients (18.3%); C3d positivity was evident in 1 patient (1.6%) and 2 patients (3.3%) had dual IgG and C3d positivity. The mean hemoglobin was $10.8{\pm}2.4gm/dl$. Significantly low mean hemoglobin of $8.3{\pm}3.0gm/dl$ was seen in Coombs positive patients compared with negative patients having a mean hemoglobin level of $11.7{\pm}1.6gm/dl$ (P<0.001). DAT positivity also demonstrated a positive association with advanced Rai stage III disease (P<0.01). No associations were noted with age, gender and biochemical markers. Conclusions: Direct Coombs test positivity in CLL in our patients, unlike in Western studies, appears relatively high, indicating significant autoimmune hemolytic anemia and advanced Rai stage in our setting. DAT positivity can be considered as a surrogative marker for advanced clinical disease.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.454-458
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• 2011

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia occurring in Western nations. In CLL it is well known that the risk of a secondary malignancy is higher than in the normal population. But in Korea, CLL is a rare type of leukemia, so there have been only a few reported cases with a secondary malignancy. CLL is characterized by progressive defects in both cell-mediated and humoral immunity. It is known that defects in the immune system of patients with CLL contribute to the development of a secondary malignancy. We experienced a case of a 71-year-old man who suffered from a chronic cough and was diagnosed with small cell lung cancer coexisting with CLL. Until this case, there was no reported case in Korea of small cell lung cancer coexisting with CLL. We now report a case of small cell lung cancer coexisting with CLL and present a literature review.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8533-8539
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• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5983-5986
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• 2015

Background: Serum 25-hydroxyvitamin D insufficiency is very common in Pakistan and is often related to inferior prognosis in some cancers but limited data exist for hematopoietic malignancies. This study was conducted to determine the vitamin D insufficiency in B-chronic lymphoid leukemia (CLL) cases at the time of presentation and its possible correlation with clinical staging, hematological parameters and biochemical markers. Materials and Methods: This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty patients with B-chronic lymphoid leukemia were enrolled. Complete blood count, vitamin D levels, serum urea, creatinine, uric acid and LDH levels were assessed. Data were compiled and analyzed using SPSS version 21. Results: Out of 60 patients, 42 (70%) were male and 18 (30%) were female. Mean age was $59.0{\pm}9.2years$. The frequency of vitamin D insufficiency was found to be 56.7%. Overall insufficiency was more frequently seen in male gender (40%). Vitamin D insufficiency demonstrated a positive association with low lactate dehydrogenase levels (P=0.005). No links were established with age, clinical stage, hematological and other biochemical markers. Conclusions: Vitamin D insufficiency is high compared with Western studies. Whether normalization of vitamin D insufficiency in deficient B-CLL patients could improve the clinical outcome or delay disease progression will require further studies.