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M Taniwaki

Publications and source records attributed to M Taniwaki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ectopic expression of MAFB gene in human myeloma cells carrying (14;20)(q32;q11) chromosomal translocations.

Chromosome 14q +, which represents a chromosomal rearrangement involving the immunoglobulin heavy chain gene (IgH) locus, is a genetic hallmark of human multiple myeloma (MM). Here, we report the identification of (14;20)(q32;q11) chromosomal translocations found in MM cells. Double color fluorescence in situ hybridization analyses pinpointed the breakpoints at the 20q11 locus in two MM cell lines within a length of at most 680 kb between the KIAA0823 and MAFB gene loci. Among the transcribed sequences in the vicinity of the breakpoints, an ectopic expression of the MAFB gene, which is located at 450 - 680 kb telomeric to one of the breakpoints and encodes a member of the MAF family basic region / leucine zipper transcription factor, was demonstrated to be associated with t(14;20). This finding, together with that of a previous study describing its transforming activity, suggests that the MAFB gene may be one of the targets deregulated by regulatory elements of the IgH gene as a result of t(14;20).

Avian Proteins↗
PubMed2001

Clinicopathologic and cytogenetic analyses of three cases of primary uterine non-Hodgkin's lymphoma.

Primary uterine non-Hodgkin's lymphoma (NHL) is an extremely rare disease. To accumulate more information on clinical data, we report three cases of primary uterine NHL with apparently the first demonstration of karyotypic analysis. Histological diagnosis was diffuse large B cell type in all patients. Two of them with advanced stage showed chemoresistance and a short survival. The remaining case with early stage showed an uneventful course following operation. No common chromosomal abnormality was detected. The therapeutic strategy for uterine NHL might therefore be similar to that for other types of aggressive NHL, although a larger study is needed.

Aged↗
PubMed2001

Establishment of CD7+ human myeloma sister cell lines, KMS-21-PE and KMS-21-BM, carrying t(11;14) and t(8;14).

Two new human myeloma cell lines were established from pleural effusion and bone marrow malignant cells derived from a single patient, who manifested hyperammonemia associated with multiple myeloma, and these were characterized. Both lines possess t(11;14)(q13;q32) and t(8;14)(q24;q32) reciprocal translocations and overexpress cyclin D1, but not c-myc. Human myeloma lines including these new lines produced and secreted excess ammonia into culture medium more than non-myelomatous hematological cell lines. In addition, these two lines were revealed to have high surface CD7 expression correlated with relatively high mRNA expression by MP-RT-PCR. Among 8 human myeloma lines, half of them revealed significant surface expression of CD7 and a positive correlation between expression levels of protein and message. CD7 message was also detected in surface negative lines. Consequently, there may be posttranslational regulation of the CD7 molecule, whose cellular biological role in expressing cells has not been elucidated.

Adult↗
PubMed2001

[Small lymphocytic lymphoma/chronic lymphocytic leukemia with t(11;14)].

A 83-year-old woman was referred to our hospital because of swollen lymph nodes, marked splenomegaly, and bone marrow abnormality. Histological examination of the lymph nodes revealed characteristic findings for small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). The immunophenotype of the tumor cells was CD5+, 10-, 19+, 20+, 23-, IgM+D+. Interphase fluorescent in situ hybridization (FISH) detected t(11;14), and immunohistochemical studies demonstrated cyclin D1 expression. In both SLL/CLL and mantle cell lymphoma (MCL), the normal counterpart of the tumor cells is thought to be CD5-positive B1 cells. The present case may therefore have been borderline between SLL/CLL and MCL.

Aged↗
PubMed2000

A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.

The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which is frequently characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and poor prognosis. Previously, the breakpoint cluster region (BCR) at 3q21 was identified within a 60-kilobase (kb) region centromeric to the BCR of 3q21q26 syndrome and that at 1p36.3 within a 90-kb region. In this study, genes were searched near the breakpoints at 1p36.3, and a novel gene was isolated that encoded a zinc finger protein with a PR domain, which is highly homologous to the MDS1/EVI1 gene. The novel gene, designated as MEL1 (MDS1/EVI1-like gene 1), with 1257 amino acid residues is 64% similar in nucleotide and 63% similar in amino acid sequences to MDS1/EVI1 with the same domain structure. The MEL1 gene is expressed in leukemia cells with t(1;3) but not in other cell lines or bone marrow, spleen, and fetal liver, suggesting that MEL1 is specifically in the t(1;3)(p36;q21)-positive MDS/AML. On the basis of the positional relationship between the EVI1 and MEL1 genes in each translocation, it was suggested that both genes are transcriptionally activated by the translocation of the 3q21 region with the Ribophorin I gene. Because of the transcriptional activation of the EVI1 family genes in both t(1;3)(p36;q21)-positive MDS/AML and 3q21q26 syndrome, it is suggested that they share a common molecular mechanism for the leukemogenic transformation of the cells.

Amino Acid Sequence↗
PubMed2000

Isolation, tissue distribution, and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene.

The gene encoding activation-induced cytidine deaminase (AID), a member of the cytidine deaminase family, was isolated from a murine B cell lymphoma line, CH12F3-2, induced by combined stimulation of TGF-beta, IL-4, and CD40L. We have isolated the human orthologue of mouse AID cDNA, which has an open reading frame of 198 residues containing a conserved cytidine deaminase motif. The amino acid sequence of human AID is 92% identical to that of mouse AID. RT-PCR analysis of 15 human tissues showed that AID mRNA is expressed strongly in lymph nodes and tonsils. The complete human AID gene consisting of five exons was isolated and mapped to chromosome 12p13 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed2000

The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma.

The BCL6 gene, isolated from the breakpoints of 3q27-associated chromosomal translocations, has been implicated in diffuse large B-cell lymphomas (DLBL). Here we describe the molecular characterization of novel t(3;7)(q27;p12) translocations in 2 patients with DLBL. Molecular genetic analysis of the breakpoint area involving BCL6 revealed the presence of the Ikaros gene, a central regulator of lymphoid differentiation that had been mapped to human chromosome 7 band p13-p11.1. As a molecular consequence of the translocation, the 5' regulatory region of the BCL6 gene was replaced by the putative 5' regulatory region of the Ikaros gene, probably leading to deregulated expression of the BCL6 gene throughout B-cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) analyses of a patient sample established that the t(3;7)(q27;p12) results in fusion of the Ikaros and BCL6 genes. This study provides the first evidence that the Ikaros gene is rearranged in human hematopoietic malignant disorders. (Blood. 2000;95:2719-2721)

Base Sequence↗
PubMed2000

Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).

The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. Genes Chromosomes Cancer 27:229-238, 2000.

Aged↗
PubMed2000

c-myc overexpression is not mandatory in aggressive-phase multiple myeloma with Burkitt's type translocation.

This report concerns a case of aggressive-phase multiple myeloma (AGMM) with Burkitt's type translocation t(8;14)(q24;q32), detected by Giemsa-banding. Double-color fluorescence in situ hybridization identified the breakpoint on 8q24 at a comparatively centromeric site, which was at least 300 kb and possibly 600 kb distant from the c-myc coding region. The breakpoint on 8q24 of the present case was far removed from that seen in other B-cell neoplasms with t(8;14)(q24;q32). Despite the presence of t(8;14)(q24;q32), neither rearrangement nor overexpression of the c-myc gene was observed in this case. Although our case may be a special case of multiple myeloma, it nevertheless suggests that overexpression of c-myc is not mandatory in an AGMM patient with Burkitt's type translocation. t(8;14)(q24;q32) which was seen in our case represents one of the first to be mapped at more than 300 kb 5' of c-myc. It should also be noted that this result could mean that a centromeric boundary 5' of c-myc exists where the influence of the immunoglobulin (Ig) H enhancer on c-myc transcription is not effective.

Aged↗
PubMed2000

Detection of t(14; 18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease.

The most frequent nonrandom chromosome rearrangements in B-cell non-Hodgkin lymphoma (NHL) is the t(14;18)(q32;q21) found in follicular lymphomas. The t(14;18) in Hodgkin disease (HD) was rarely observed using cytogenetic techniques. Although Southern blot analysis failed to demonstrate the t(14;18), there have been conflicting reports concerning the occurrence of the translocation using polymerase chain reaction (PCR) methods in HD. In some HD tissues, the translocation might be derived from background lymphocytes rather than Hodgkin and Reed-Sternberg (HRS) cells, because B-cells with t(14;18) are regularly generated in normal individuals. However, the cells bearing the translocation have remained unidentified. We describe a patient with HD who showed t(14;18) in hyperdiploid cells using fluorescence in situ hybridization (FISH) and HRS cells which were strongly positive for BCL2 by immunohistochemistry. These findings suggest that HRS cells may have a t(14;18).

Adult↗
PubMed2000

Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies.

The immunoglobulin (Ig) genes are frequently involved in chromosomal rearrangements with a wide variety of partner loci in multiple myeloma (MM). However, several partner chromosomes have not been detected by conventional cytogenetic methods; for example, 4p16.3 (FGFR3), 6p25.3 (IRF4), and 16q23 (c-maf). To clarify the incidence of t(4;14)(p16.3;q32.3) in primary tumors of MM and to evaluate possible correlations with specific manifestations of the disease, G-banding, double-color fluorescence in situ hybridization (DC-FISH), and/or reverse-transcriptase polymerase chain reaction (RT-PCR) were performed on 40 patients with MM-two with plasmacytoma (PCM) and three with plasma cell leukemia (PCL). All patients were studied by DC-FISH; 40 were studied by G-banding and 36 were studied by RT-PCR. The FISH probes consisted of a cosmid pC385.12 containing the FGFR3 gene, a YAC Y6 containing VH, and a phage Iggamma1-10 containing the gamma1 constant region (Cgamma). We identified eight patients with either FGFR3/Cgamma fusion or FGFR3 overexpression: six patients with both FGFR3/Cgamma fusion and FGFR3 overexpression, one patient with FGFR3/Cgamma, and one with FGFR3 overexpression. FGFR3/Cgamma fusion was demonstrated at a frequency of 19% to 38% on interphase nuclei in seven of the 45 patients. Lytic bone lesions were found to be associated with FGFR3 overexpression. Interphase FISH with FGFR3 and Cgamma probes combined with RT-PCR proved to be an effective tool for detection of this fully cryptic translocation, thus facilitating the characterization of clinical features of MM patients with t(4;14).

Adult↗
PubMed2000

Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene.

We report here a 65-year-old man with a myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. He had received chemotherapy with tegafur for renal carcinoma. Chromosome analysis of bone marrow cells revealed complex karyotypes; del(5)(q13) was observed in all 20 metaphase spreads, and two related aberrations, add(12)(p11) and add(12)(p13), were detected in 13 and 7 cells, respectively. Fluorescence in situ hybridization (FISH) analysis with chromosome-specific DNAs revealed that these alterations originated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q13), add(12)(p11), and add(12)(p13) were revised as der(5)t(5;12)(q13;p13), der(12)del(12)(p11p13)t(5;12)(q13;p13), and der(12)t(5;12)(q13;p13), respectively. Fluorescence in situ hybridization with a series of cosmid probes spanning the ETV6 gene showed that the 12p13 breakpoint on the der(12)t(5;12)(q13;p13) was located in intron 1, but the exon 1 signal was deleted. Our results suggest that a fusion gene was generated between the 5'-end of an unidentified partner at 5q13 and the 3'-end of ETV6 by t(5;12)(q13;p13), and that the interstitial deletion (12)(p11p13) occurred following t(5;12) during clonal evolution. del(12)(p11p13), including the rearranged ETV6 gene, may be implicated in the progression of MDS.

Aged↗
PubMed2000

Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6.

Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear. Reactive oxygen species released by polymorphonuclear leukocytes and macrophages are factors causing DNA damage in the foci of inflammation, and thus could play a role in lymphomagenesis. The xanthine/xanthine oxidase (X/XOD) system produces a mixture of hydrogen peroxide and superoxide anion extracellularly, and thus serves as an in vitro source of reactive oxygen species. Cell death of lymphoblastoid cell lines (LCLs) was induced with X/XOD treatment in a dose-dependent manner. DNA fragmentation, which is the characteristic feature of apoptosis, was observed in LCLs at 4-8 hours after X/XOD treatment. Among cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma, only pretreatment with IL-6 gave LCLs the resistance to X/XOD-induced cell death in a dose-dependent manner. The proportion of apoptotic cells in X/XOD-treated LCL culture was decreased with IL-6 pretreatment by quantification with flow cytometric analysis. Treatment of LCLs with IL-6 for 48 hours up-regulated bcl-2 mRNA expression. Furthermore, the LCLs repeatedly treated with X/XOD and cultured with or without IL-6 showed many more structural abnormalities of chromosomes than those without X/XOD treatment. Colony forming efficiency of X/XOD-treated LCLs with IL-6 was significantly higher than those without IL-6, and even relatively higher than LCLs without X/XOD treatment. IL-6 could support the survival of non-neoplastic B cells and accelerate the malignant transformation of B lineage cells in inflammatory lesions.

Apoptosis↗
PubMed2000

Myelodysplastic syndrome with clonal eosinophilia accompanied by eosinophilic pulmonary interstitial infiltration.

We report a case of de novo myelodysplastic syndrome with clonal eosinophilia (MDS-Eo) and eosinophilic pulmonary interstitial infiltration, confirmed by autopsy. Cytogenetic study using Giemsa banding identified 47,XY,+1,der(1;7)(q10;p10),+8 in the marrow cells. Simple Giemsa staining revealed the same chromosomal aberration in metaphase spreads with eosinophilic granules, indicating the clonal proliferation of eosinophils. To our knowledge, our case is the 6th reported case of MDS-Eo with cytogenetically confirmed clonal eosinophilia, and the first autopsy of MDS-Eo. A review of the literature combined with our findings suggests that this type of chromosomal aberration might be involved in the as yet unknown pathogenesis of MDS-Eo.

Aged↗
PubMed2000

Randomized comparison of mobilization kinetics of circulating CD34+ cells between biweekly CHOP and dose-escalated CHOP with the prophylactic use of lenograstim (glycosylated rHuG-CSF) in aggressive non-Hodgkin's lymphoma. The lenograstim/Lymphoma Study Group.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation has been expected to result in a promising outcome in high risk aggressive non-Hodgkin's lymphoma (NHL). However, it remains unknown what type of initial chemotherapy is optimal, especially regarding progenitor cell mobilization. Sixty-three untreated patients with aggressive NHL in a high risk group were randomized to either a biweekly arm with 8 cycles of standard CHOP or 6 cycles of the dose-escalated CHOP arm with cyclophosphamide 1.5 g/m2 and doxorubicin 70 mg/m2. Lenograstim (glycosylated rHuG-CSF 2.0 microg/kg/day) was administered daily from day 3 to patients in both arms. The mobilization effect of the two regimens on circulating CD34+ cells was evaluated. Twenty-seven of 29 patients in the biweekly CHOP arm and 33 of 34 patients in the dose-escalated CHOP were assessable. Dose-escalated CHOP yielded a significantly higher number of circulating CD34+ cells in the first cycle compared with biweekly CHOP (p=0.05). The peak number of circulating CD34+ cells with biweekly CHOP did not significantly change from cycle to cycle; however, in dose-escalated CHOP, the peak number of circulating CD34+ cells mobilized after the fifth and sixth cycle was lower than after the first cycle (p=0.07 and 0.009, respectively). Routine conventional-dose chemotherapy and low-dose G-CSF can mobilize sufficient CD34+ cells in patients with aggressive NHL. The mobilization kinetics of circulating progenitor cells in patients with aggressive NHL is dependent on the dosage and schedule of CHOP.

Adjuvants, Immunologic↗
PubMed2000

The p73 gene is less involved in the development but involved in the progression of neuroblastoma.

We performed expression, mutation, loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analyses of the p73 gene in neuroblastomas (NBs). Reverse transcription-polymerase chain reaction (RT-PCR) using primers which can detect both the p73alpha and p73beta transcripts was performed on 30 fresh NBs and 22 NB cell lines. Aberrant expression of the p73 gene was found in 4 (25%) of 16 primary tumors found by mass screening and in 10 (71.4%) of 14 primary tumors found clinically. The rates of expression in these two types of tumors were significantly different (p=0.026, Fisher's exact test). The incidence of aberrant expression of the p73 gene was significantly higher in stage IV patients than in stages I, II, III plus IVS patients (p=0.0236, Fisher's exact test). No homozygous deletions or rearrangements of the p73 gene were found in any samples examined. In addition to the polymorphism in exon 2, a silent mutation (codon 336 GCC/GCT) was found in one primary tumor. LOH of the p73 gene was detected in 5 (15%) of 33 primary NBs using PCR-LOH analysis. FISH analysis showed that all 17 NB cell lines used in this study revealed allelic loss of the p73 gene, while most of them expressed the p73 gene. These results suggest that the p73 gene is not monoallelically expressed in NB. We conclude that the p73 gene is less involved in the development but involved in the progression of neuroblastoma.

DNA Primers↗