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M Takishita

Publications and source records attributed to M Takishita.

10 recordsLinked to original sources
PubMed1995

Frequent somatic mutations in D and/or JH segments of Ig gene in Waldenström's macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter's syndrome but not in common CLL.

V(D)J recombination and somatic hypermutations are developmentally regulated during B-cell differentiation; therefore, DNA analysis of the Ig gene delineates the cellular origin of B-cell neoplasms. We analyzed the third complementarity-determining region and adjacent regions of the Ig heavy-chain gene of tumor cells from 7 patients with Waldenström's macroglobulinemia (WM) and from 10 patients with B-cell chronic lymphocytic leukemia (CLL), 2 of whom progressed to high-grade non-Hodgkin's lymphoma (NHL), ie, Richter's syndrome (RS). There were no intraclonal variations resulting from VH replacements or ongoing somatic mutations in both WM and CLL. We found replacement mutations in the D and/or JH segments in all patients with WM and in 4 of the 10 patients with CLL, including the 2 RS patients. Replacement mutations were clustered in codon 102 of the JH segment. Preferential utilization of the JH4 gene was found in WM (5 of 7 [71.4%]) and in CLL (7 of 10 [70.0%]), and DXP family genes in CLL (5 of 10 [50.0%]). In conclusion, WM and CLL with RS are generated under the influence of antigenic stimulation and selection. However, the majority of CLL may arise from a distinct subpopulation that has the restricted repertoire of nonmutated Ig genes.

Adult↗
PubMed1995

Multiple myeloma: new evidence and insights from the immunoglobulin heavy chain gene and phenotypes.

DNA analysis of the Ig genes has been utilized to delineate the stages of differentiation of normal and malignant B-lineage cells, since the mechanisms involved in V(D)J recombination, somatic hypermutations, and class switch are developmentally regulated. Somatic mutations which result in amino acid substitutions are observed frequently in the Ig variable region genes in multiple myeloma (MM), but there is no intraclonal variation. This fact suggests that the target cell of malignant transformation in MM is a B-lineage cell which already has undergone antigenic selection. This B-lineage cell probably corresponds to a pre-plasma cell or a plasma cell rather than a memory B cell. Tumour cells which share an identical third-complementarity-determining-region (CDR3) sequence with the myeloma cells can be detected from the various fractions representing different stages of B-cell differentiation, such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- cells from the peripheral blood. Thus, the tumour cells in MM are composed of immunophenotypically heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM. Dedifferentiation to the stem cell level may be essential to the malignant transformation in MM.

Base Sequence↗
PubMed1995

[Advances in biology and pathogenesis of multiple myeloma].

Plasma cell malignancy, multiple myeloma, is the prototype of monoclonal terminal-differentiated B cell proliferation that reveals a monoclonal Ig in the serum and/or urine of the majority of patients. New insights into the biology and pathogenesis of this entity are based on careful research to a complex cytokine network including TNF beta, IL-1 beta, and IL-6, many oncogene products such as bc1-2 protein, H-ras p-21 protein, and RB-1 product, and cell surface antigens associated with myeloma cells. The recent understanding on the mechanism for acquisition of IgV region diversity during B cell development has clarified the origin of the clonogenic cell in multiple myeloma. Further identification of new prognostic parameters as well as new therapeutic agents is necessary for the rational therapy of this refractory malignancy.

Aged↗
PubMed1994

A novel membrane antigen selectively expressed on terminally differentiated human B cells.

A monoclonal antibody (MoAb) that defines a novel terminal B-cell-restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenström's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig-secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non-plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Animals↗
PubMed1994

Cellular origin and extent of clonal involvement in multiple myeloma: genetic and phenotypic studies.

The cellular origin and extent of clonal involvement in multiple myeloma (MM) are controversial. The third-complementarity-determining region (CDR3) of the immunoglobulin heavy chain gene is the target region of VH replacements and somatic mutations. We analysed the CDR3 sequences of myeloma cells from eight newly diagnosed and three relapsed patients in order to elucidate the target cell of malignant transformation in MM. We also examined the extent of clonal involvement in MM using a CDR3 clone-specific nucleic acid probe. The peripheral lymphocytes from the five MM patients were separated into fractions such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- and CD2+ cells. Amplified CDR3 DNAs from these subpopulations were hybridized with the probe specific to each patient's tumour cells. We found no evidence of ongoing VH replacements or somatic mutations in CDR3 in MM. However, frequent nucleotide mutations in D and JH segments were observed. Circulating malignant cells were detected in the CD34+ and all of the CD20+ subpopulations, but not in the CD2+ fraction. MM is a neoplasm originating from a B-lineage cell which has already undergone antigen-dependent selection. Nevertheless, the tumour cells are composed of heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. Conversely, T cells were not involved in MM. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM.

Aged↗
PubMed1992

Primary adult T-cell lymphoma of the breast.

A case of primary adult T-cell lymphoma (ATL) of the breast is described. A 69-year-old woman presented with a painless, rapidly growing lump in her left breast. Staging procedures demonstrated no sign of generalized disease. Following a Patey's mastectomy, 10 courses of adjuvant chemotherapy (CHOP) were successfully administered. The light microscopic, immunohistochemical and molecular genetic analyses of the surgical specimen revealed a primary ATL. Seropositive mothers who breast-feed their children may facilitate the accumulation of T cells carrying HTLV-I in their breasts and thereby increase their risks of developing breast ATL.

Aged↗
PubMed1992

[Malignant histiocytosis with T cell receptor and immunoglobulin gene rearrangements].

A case of malignant histiocytosis with rearrangements of both T-cell receptor and immunoglobulin genes. The patient was a 69 year-old woman suffering from high fever, which was unresponsive to the administration of various antibiotics and steroids for more than two weeks. Laboratory findings on admission revealed disseminated intravascular coagulopathy and liver dysfunction. The bone marrow examination showed an increased number of giant cells. Some of the giant cells had phagocytosis of various blood cells and were cytochemically stained with non-specific esterase, but not with myeloperoxidase and PAS. Immunohistochemical study revealed that alpha 1-antitrypsin alpha 1-antichymotrypsin, lysozyme and CD15 were all detected in the cytoplasm of some giant cells while CD30 was not detected. Of interest was the rearrangements of the T-cell receptor, Ig heavy chain and kappa chain genes on bone marrow mononuclear cells demonstrated by Southern blot analysis.

Aged↗
PubMed1990

[Myelodysplastic syndrome (RAEB-T) occurring after adjuvant chemotherapy for colon and rectum cancers].

A 67-year-old man was admitted to our hospital because of bleeding tendency and high fever. The patient had a past history of gastrectomy and transverse colectomy for cancer of transverse colon at age 57, and rectum resection for rectum cancer at age 59. After these operations, Tegafur 645 g, MMC 56 mg, and Ara-C 560 mg were administered for about 6 years. Hematological examinations revealed hemoglobin of 7.7 g/dl, white cell count of 9,500/microliters with 8% myeloblasts, and platelet count of 7,000/microliters. A diagnosis of myelodysplastic syndrome (RAEB-T) was made from the finding of bone marrow smear, which showed 28% myeloblasts, and neutrophils and megakaryocytes with morphologically abnormal nuclei and cytoplasms. Chromosomal banding study of the bone marrow cells revealed -5, -8, 7q- in all analyzed cells. These findings suggest that the preceding adjuvant chemotherapy is probably related to the occurrence of myelodysplastic syndrome.

Aged↗