Human T lymphotropic virus type I (HTLV-I) impairs cellular immunity and can develop into adult T cell leukemia/lymphoma (ATLL). The Role of dendritic cells (DC) has not been fully elucidated in individuals infected by HTLV-I. To address this issue, we studied several cellular parameters, including phenotypic and functional characteristics of monocyte-derived DC. Generated DC exhibited down-regulation in the expression of CD1a and HLA-DR in HTLV-I carriers, suggesting partial impairment of maturation. T cells were stimulated by autologous DC in half of HTLV-I carriers, as well as healthy donors, but not in ATLL patients. Because of the importance of CD40-CD40 ligand (CD40L) signaling in establishing an inflammatory immune response, we also investigated the expression of soluble CD40L (sCD40L) of PHA-activated lymphocytes from HTLV-I infected individuals. sCD40L was detected in the culture supernatant of lymphocytes from one of four HTLV-I carriers investigated. These results suggest that the defect or aberration in the function of DC and the expression of sCD40L in T cells is associated with immune suppression in HTLV-I infected individuals.
The effect of G-CSF on leukemic stem cells, which can support the long-term proliferation of leukemic cells in vivo, needs to be clarified to confirm the long-term safety of clinical use of G-CSF. When we examined the effect of G-CSF on leukemic stem cells in NOD/SCID mice using a transplantation assay, the engraftment of leukemic cells derived from 8 AML cases was neither supported by G-CSF alone, nor enhanced by G-CSF plus GM-CSF, IL-3 and SCF. These findings suggest that G-CSF was not able to stimulate leukemic stem cells into maintaining the long-term proliferation of leukemic cells in vivo.
We studied 48 patients with multiple myeloma and its related disorders (plasma cell dyscrasias: PCD). Clonal changes were observed in 19 patients (39.6%), which included 9 untreated and 10 treated patients. Chromosomal gains of 3, 11 and loss of 13 were the most frequent numerical chromosome aberrations. Chromosome 13 was lost at an early stage and 17p (p53) abnormality appeared in an advanced stage of the disease. The most common additional region was lq which contained a locus of the IL-6 receptor gene instead of 7p, the locus of the IL-6 gene. The break points were clustered at 1p13, 6q21, 7p11.2 14q32, 17p11 and 19p13.3, which were the loci of protooncogenes, tumor suppresser genes or immunoglobulin-related genes. Three patients showed a balanced translocation of t (11; 14) (q13; q32). The characteristic features of chromosomal changes in PCD were frequent chromosomal gains and losses and rare balanced translocations. These findings are similar to those found in secondary leukemias and solid tumors, rather than de novo leukemias.
Epstein-Barr virus (EBV) is a ubiquitous virus that infects more than 90% of the world's population. In Malaysia this virus has been well documented in patients suffering from nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt's lymphoma. This study investigated the viral subtype and variant through the latent membrane protein-1 (LMP-1) gene taken from EBV-infected cancers in Malaysian patients. Nested polymerase chain reaction assays of EBV nuclear antigen-2 and single step polymerase chain reaction on the C-terminus of the LMP-1 gene were performed for virus typing and detection of a 30-bp deletion, respectively. Samples were obtained from 39 cases of nasopharyngeal carcinoma, 48 cases of Hodgkin's lymphoma, 19 cases of Burkitt's lymphoma and 19 cases of non-neoplastic reactive lymphoid tissues. All the tumors harbored EBV type A. Both the deleted and non-deleted variants were observed in the malignant tissues. In some cases, there was concurrent dual expression of both variants. Statistical analysis showed a significantly higher percentage of 30-bp deletions in cases of malignancies compared to reactive tissues. In conclusion, EBV type A predominates in Malaysian cancers, with a significant representation of the 30-bp deleted variant.
We present morphologic, immunohistochemical and molecular profiles of signet ring cell lymphoma (SRCL). The lymph node removed showed a diffuse infiltration of lymphoma cells consisting of large blastic cells (LBC)and signet ring cells (SRC). LBC had a large oval-shaped nucleus, occasionally with one or more nucleoli and scant cytoplasm, while SRC possessed eosinophilic cytoplasmic inclusions (Russell bodies) that displaced and distended the nucleus. LBC were CD20+, CD79a+, CD138- and CD10-. SRC were CD20-, CD79a+, CD138+ and CD10-. Both LBC and SRC contained the same monoclonal cytoplasmic immunoglobulin(IgG, γ). Anti-CD 21 and anti-CD23 antibodies failed to stain the proliferative areas of the lymphoma cells. Somatic mutation and intraclonal microheterogeneity of the rearranged immunoglobulin heavy chain (IgH) gene variable region (VH gene) were examined. The VH gene exhibited 99% homology to the closest germline and no intraclonal microheterogeneity was found. These data revealed that the lymphoma cells possessed a class-switched IgH gene with little somatic mutation of the VH. This case is not a variant of follicular lymphoma derived from germinal center cells, but a variant of immunoblastic lymphoma derived from post germinal center cells.