|Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
Hairy B-cell lymphoproliferative disorder (HBLD) is a new disease entity, characterized by chronic polyclonal B-cell lymphocytosis with features resembling hairy cell leukemia (HCL)-Japanese variant.
1. Various cytokines and mitogens failed to induce proliferation and differentiation in B-cells in HBLD (HBLD cells) but TNFα and SAC, which slishtly enhanced the ^3H tymidine uptake.
2. HBLD cells did not differentiate into Ig-secreting cells by phorbol ester (TPA), but changed their shape into fibroblast-like cells, as described for HCL cells. Y27632, an inhibitor of ROCK, suppressed this transformation. We also studied effects of wortmannin, a PI3 kinase inhibitor, on the morphology of HCL cells and HBLD cells. The studies suggested association of Rho and Rac/Cdc42 with the characteristic morphology of these cells.
3. We previously showed that ubiquitin (Ub) was secreted from HCL cells and had inhibitory effects on normal hematopoiesis. In this study, we investigated effects of extracellar
Ub on various hematopoietic cell lines. The results suggested that extracellar Ub incorporated into hematopoitic cells and mediated growth suppression and apoptosis through a proteasome-dependent manner. We also found that serum Ub levels were higher in patients with HBLD than in normal volunteers, suggesting that Ub may be involved in anemia and/or thrombopenia seen in those with HBLD.On the other hand, Ub showed no effect on differentiation and proliferation of HBLD cells.
4. Clinical and hematological resemblance of HBLD and HCL-Japanese variant suggests that HBLD may transform into HCL.We detected small B-cell clones in peripheral blood lymphocytes or spleen cells from two of 7 patients with HBLD by PCR.Chromosomal abnormality was detected in one patient. The B-ceLl clones persisted, but expansion of the clones was not seen.
5. Attempts were made to detect known or unknown viruses, and immunological abnormalities including those of cytokines in HBLD, but we could not find any causative factor of the disease. Less