• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5341-5344
• /
• 2013

Objectives: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). Methods: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. Results: From age group 10-19 years to age group ${\geq}60$ years, the percentage of LC decreased from $67.0{\pm}18.4%$ to $49.0{\pm}25.1%$ (F=2.353, P=0.041). LC percentage was higher in patients with balanced karyotypes ($65.7{\pm}22.4%$), than those with unbalanced karyotypes ($46.0{\pm}26.6%$) (u=3.444, P=0.001) or a normal karyotype ($49.9{\pm}22.1%$) (u=5.093, P<0.001). Patients with FLT3-ITD ($64.3{\pm}19.5%$) had higher LC percentages compared with those without ($54.2{\pm}24.3%$) (u=2.794, P=0.007). Conclusions: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.

• KSBB Journal
• /
• v.27 no.5
• /
• pp.295-300
• /
• 2012

Matured dendritic cells (DCs) begin migration with their release from the bone marrow (BM) into the blood and subsequent traffic into peripheral lymphoid and non-lymphoid tissues. Throughout this long movement, migrating DCs must apply specialized skills to reach their target destination. Non-invasive in vivo cell-tracking techniques are necessary to advance immune cell-based therapies. In this study, we used a DiD cell-tracking solution for in vivo dendritic cell tracking in naive mice. We tracked DiD (non-invasive fluorescence dye)-labeled mature dendritic cells using the Near Infrared (NIR) imaging system in normal mice. We examined the immunophenotype of DiD-labeled cells compared with non-labelled mature DCs, and obtained time-serial images of NIR-DC trafficking after mouse footpad injection. In conclusion, we confirmed that DiD-labeled DCs migrated into the popliteal lymph node 24 h after the footpad injection. Here, these data suggested that the cell tracking system with the stable fluorescence dye DiD was useful as a cell tracking tool to advance dendritic cell-based immunotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.16
• /
• pp.7343-7350
• /
• 2015

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.

• Archives of Plastic Surgery
• /
• v.35 no.3
• /
• pp.229-234
• /
• 2008

Purpose: There are some reports presenting that peripheral blood contain circulating hematopoietic cells as well as, in significantly smaller quantities, mesenchymal stem cells. The purposes of this study is to isolate and characterize circulating mesenchymal progenitor cells with osteogenic potential from human peripheral blood. Methods: Human buffycoat containing mononuclear cells was harvested from peripheral blood of normal persons and isolated using a density gradient centrifugation and serially subcultured in osteogenic media for 1-4 weeks. The proliferation capability, phase-contrast microscopy, transmission electron microscopy, immunophenotype FACS analysis, Alizarin red staining and RT-PCR assays for osteogenic differentiation potential were performed. Results: The phenotype of cultured cells changed from small round or cuboidal cells at passage 1 into large spindle-shaped fibroblastic morphology cells at passage 4. Surface marker expressed CD14, but did not express CD34, CD80, CD83. Strong positive staining was observed for Alizarin reds in osteogenic medium on day 14, Using RT-PCR, the mRNA levels of bone- specific genes, such as ALP, c-bfa-1 and osteocalcin were detected. Conclusion: A new subset of peripheral blood derived progenitor cells described here has the ability to proliferate and differentiate into osteogenic cell lineages in vitro, and to be candidate for regenerative therapy.

• Clinical and Experimental Pediatrics
• /
• v.46 no.12
• /
• pp.1266-1270
• /
• 2003

The advance of the immunobiology clarifies the nature of non-Hodgkin's lymphoma(NHL). In addition the proceed in the immunophenotyping renders the classification of NHL. According to the Revised European American Lymphoma(REAL) classification, classified by the etiologic factors, molecular biological characteristics, immunophenotype, cytogenetics and histologic feature, nasal T/NK-cell lymphoma(=angiocentric lymphoma) belongs to the category of peripheral T-cell and natural killer cell lymphoma. Nasal T/NK-cell lymphoma is a distinct clinicopathologic entity characterized by progressive necrotic lesions in the nasal cavity, nasopharynx, and palate. The cellular origin of this tumor has been controversial. Although most nasal T/NK-cell lymphomas are of NK-cell lineage, being CD56+, negative for surface CD3(Leu4), and unassociated with rearrangements of the T-cell receptor genes, other minor variants have been reported. This lymphoma is a rare disease and usually experienced in adult. Recently, we experienced a rare type lymphoma, nasal T/NK-cell lymphoma, in 14 years old boy. His soft mass occupied the right nasal cavity including the nasal septum and turbinate. Pathologically this nasal mass showed the infiltration into the vascular wall, illustrating angiodestructive lesion. The cellular origin was NK-cell lineage, being CD56+ and negative to CD3. Now, we report the case with a brief review of related literatures.

• IMMUNE NETWORK
• /
• v.4 no.2
• /
• pp.88-93
• /
• 2004

Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

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

• Clinical and Experimental Pediatrics
• /
• v.50 no.7
• /
• pp.601-605
• /
• 2007

The cure rate of acute lymphoblastic leukemia (ALL) in children dramatically improved over past 5 decades from zero to about 80%. The main cause of improvement is owing to the development of chemotherapy by multicenter clinical trial of large study groups with the understanding of leukemia biology. Recently, pediatric ALL protocols were applied to the treatment of adolescent and even adult ALL patients. For nearly 30 years, clinical factors have been used to risk-stratify therapy for children with ALL, so that the most intensive therapies are reserved for those patients at the highest risk of relapse. The risk groups of ALL are divided as standard- (low- plus intermediate-), high- and very high-risk group according to the prognostic factors, and treatment results improved by this risk based treatment. The factors used to risk-stratify therapy include age, gender, presenting leukocyte count, immunophenotype, cytogenetic aberrations including ploidy and translocations, and initial response after 1 to 2 weeks of therapy. But treatment efficacy is the most important determinant and can abolish the clinical significance of most, if at all, prognostic factors. Today, in the era of intensive, multiagent regimens, there is increasing evidence that we have reached the limits of prognostic significance of currently applied clinical risk factors in childhood ALL. As the cure rate of ALL is about 80%, introducing new prognostic factors such as new molecular prognostic markers, new methods of assessment about minimal residual disease, and pharmacogenetic study, with the development of stem cell transplantation and molecular targeted therapy are needed to cure residual 20% of childhood ALL patients without short and long term complications.

• Parasites, Hosts and Diseases
• /
• v.50 no.4
• /
• pp.301-308
• /
• 2012

In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of $CD19^+$ B cells was observed as early as week 1 post-infection while $CD4^+/CD8^+$ T cells were down-regulated. Accumulation of $Mac1^+$ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-${\alpha}$ mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-$1{\beta}$ expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-${\beta}$ were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-${\beta}$ and IL-4 during the early stages of infection.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.31 no.4
• /
• pp.316-321
• /
• 2005

Ameloblastoma is the most common odontogenic tumor of the jawbones, but the origin of this tumor has been remained to be unproven. Cytokeratins (CKs) are specific intermediate filament of epithelial cells, and vimentin is expressed in mesenchymal cells. The immunohistochemical detection of different CKs and vimentin has made it easier to know the origin of tumor. Paraffin-embedded tissue sections from 15 ameloblastomas and 1 ameloblastic carcinoma were used for immunohistochemical evaluation of CK 7, 8, 13, 14, 19 and vimentin. Their expression is evaluated in different tumor cells, which are observed in different type of tumors. In the follicular and reticular subtype, central stellate cells of tumor nests expressed CK 8, 14, 19 and peripheral columnar cells expressed CK 14. CK 7, and 13 were not expressed. Vimentin was detected in fibrous stroma around tumor nest, not in tumor cells. The tumor cells of ameloblastic carcinoma expressed CK 7, 14 and 19, but CK 8 was more weakly stained than that in ameloblastoma. Central stellate cells and peripheral columnar cells of acanthomatous subtype showed same expression pattern with others. Meta plastic squamous cells expressed CK 8, 14, 19 and keratinizing squamous cells expressed CK 13, 19. CK 7 and vimentin were not detected in tumor cells and vimentin was expressed in fibrous stroma. Most of the tumor cells of ameloblastoma showed CK 14 and CK 19 and did not express CK 7 and vimentin. These findings were similar to the immunophenotype of dental lamina. And these results will be beneficial to differential diagnosis of odontogenic tumors and other kind of tumors arising at the oral cavity.