Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy.

Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab.

Establishment of a stroma-dependent human acute myelomonocytic leukemia cell line, NAMO-2, with FLT3 tandem duplication.

We have established a stroma-dependent myelomonocytic cell line, NAMO-2, with FLT3 internal tandem duplication (FLT3/ITD). Leukemia cells from a patient with acute myelomonocytic leukemia were administered to form subcutaneous tumors in nude mice, which were maintained successively, although we failed to establish continuously growing cells from the original leukemia cell culture. In the cultures of cells from subcutaneous tumors, there were stroma cells that had originated from the nude mice and showed continuous growth.

Increased oxidative DNA products in patients with acute promyelocytic leukemia during arsenic therapy.

Arsenic trioxide (ATO) has been used to treat acute promyelocytic leukemia (APL), but the oxidative DNA damage occurring in patients has not been fully elucidated. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most abundant oxidative products of DNA, by enzyme-linked immunoassay, and reactive oxidative species (ROS), by luminol- and luminol-H2O2 chemiluminescence, in the plasma of four APL patients treated with ATO. After six courses of ATO therapy, the plasma 8-OHdG concentration had increased from 45.

Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene.

We established a leukemia cell line derived from therapy-related acute myeloid leukemia with the t(11;19) by xenotransplantation into the NOD/SCID mouse with IL-2Rgamma(c)-/- (NOG mouse). The cell line, TRL-01, could be serially transplanted from mouse to mouse and also grown in an adherence-dependent manner on a murine bone marrow stroma cell line, HESS-5. TRL-01 had the same immunophenotype as the original leukemia cells: positive for CD13, CD33, CD11a, CD18, CD29, CD49d, CD49e, CD54, CD62L, and CD117, and negative for CD3, CD4, CD8, CD19, CD34, CD41a, CD41b, CD135, and myeloperoxidase.

Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia.

Although FLT3 mutations are essentially found in myeloid-lineage leukemia cells, a high level of FLT3 expression was recently observed in MLL gene-rearranged acute lymphoblastic leukemia without FLT3 mutations. Here, we analyzed the biologic and clinical significance of the FLT3 transcript level in comparison with several gene alterations in 181 de novo acute myeloid leukemia (AML) cases. The mean expression level in AML was higher than that in normal mononuclear cells, whereas the range varied widely.

A xeno-transplantable plasma cell leukemia line with a split translocation of the IgH gene.

A novel cell line, SACHI, was established from a pericardial effusion developed during the course of primary plasma cell leukemia (PCL). The cell line SACHI cells were the same as the infiltrating plasma cells with regard to surface markers (CD38(+)CD19(-)PCA-1(+)VLA-5(-)CD56(-)TdT(+)) and immunoglobulin gene rearrangements. Analysis of SACHI cells showed a complex hypertriploid (karyotype mode 70-73) including 7p32, 14q32, and Xq24 structural abnormalities, which were found also in the original leukemia cells.