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N Maseki

Publications and source records attributed to N Maseki.

At least 19 recordsLinked to original sources
PubMed2000

Practical utility of the revised European-American classification of lymphoid neoplasms for Japanese non-Hodgkin's lymphomas.

A clinicopathological study of 515 non-Hodgkin's lymphoma (NHL) cases was performed using the revised European-American classification of lymphoid neoplasms (REAL classification) in an HTLV1-nonendemic area of Japan. The following characteristics were revealed: 1) frequency of extranodal lymphomas was high (59%) with 79% B-cell lymphomas in this series, while the overall ratio of B:T/NK lineage was 3.7:1; 2) the most common type was the diffuse large B-cell lymphoma (46%), follicle center lymphomas occurred at an incidence lower (15%) than that in European and American populations, and marginal zone B-cell lymphomas accounted for as much as 12%; 3) peripheral T-cell lymphomas were common (19%), with the unspecified type predominant (11%), while adult T-cell lymphomas were present at a level equivalent to that among European and American patients (1%). Clear segregation of survival curves was rated according to cell lineage and B-cell lymphomas had a better prognosis than T / NK-cell lymphomas. Furthermore, new subtypes in the REAL classification, such as marginal zone B-cell and mantle cell lymphomas, exhibited distinct curves. Taken altogether, the REAL classification demonstrated advantages for assessment of Japanese NHL cases.

Adolescent↗
PubMed2000

Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors.

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.

Adult↗
PubMed1999

Disomy 1 with terminal 1p deletion is frequent in mass-screening-negative/late-presenting neuroblastomas in young children, but not in mass-screening-positive neuroblastomas in infants.

The mass screening (MS) of neuroblastoma has been undertaken in Japan by measuring urinary catecholamine metabolites in infants at the age of 6 months. To clarify the biological characteristics of MS-positive (MS+) tumors in infants and MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas. The 246 tumors were classified into 4 groups on the basis of the constitution of chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p group (3/164) (p < 0.0001). Event-free survival at 5 years was lowest [19.5%; 95% confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8) groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p group (p < 0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and 55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS program into reducing mortality from neuroblastoma.

Aneuploidy↗
PubMed1999

Correlation of chromosome abnormalities with presence or absence of WT1 deletions/mutations in Wilms tumor.

Of 40 Wilms tumors with chromosome abnormalities, 6 were hypodiploid, 10 were pseudodiploid, 7 were hyperdiploid with 47 to 49 chromosomes, and 17 were hyperdiploid with 50 or more chromosomes, mostly including +12. WT1 deletions/mutations were found in one hypodiploid, eight pseudodiploid, and one hyperdiploid (47-49 chromosomes) tumor, but in none of the hyperdiploid (> or =50 chromosomes) tumors. Of the 10 tumors with WT1 abnormalities, 6 had a homozygous WT1 deletion, 1 had a nonsense WT1 mutation and loss of heterozygosity at 11p, 1 had an intragenic hemizygous WT1 deletion without detectable WT1 mutation, and 2, which occurred in Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients, had a hemizygous deletion and a missense or frameshift mutation of WT1. Six of the nine tumors with homozygous or hemizygous WT1 deletions had chromosome aberrations involving chromosome band 11p13 in one of the two chromosomes 11. While one hypodiploid and one pseudodiploid patient died of the disease, and one hyperdiploid (47-49 chromosomes) patient was alive in nonremission, all hyperdiploid (> or =50 chromosomes) patients had no evidence of disease at the last follow-up. Our data show that chromosome aberrations are closely correlated to WT1 abnormalities and suggest that hyperdiploid (> or =50 chromosomes) Wilms tumors may be characterized by the absence of WT1 abnormalities and possibly also by a favorable prognosis.

Aneuploidy↗
PubMed1999

Mixed-lineage leukemia with t(10;11)(p13;q21): an analysis of AF10-CALM and CALM-AF10 fusion mRNAs and clinical features.

A fusion transcript of AF10 and CALM was isolated recently from the U937 cell line with t(10;11)(p13;q21). We performed reverse transcription-polymerase chain reaction and sequencing analysis on the t(10;11) leukemia samples obtained from four patients and one cell line, and we identified reciprocal fusion transcripts of AF10 and CALM in all the samples. The fusion transcripts in the five samples showed four different breakpoints in AF10 and three different breakpoints in CALM. In addition, the fusion transcripts in one sample showed a nucleotide sequence deletion in AF10, and those in two samples showed a nucleotide sequence deletion in CALM; the deletions were thought to be caused by alternative splicing. The variety of breakpoints and splice sites in the two genes resulted in five different-sized AF10-CALM mRNAs and in four different-sized CALM-AF10 mRNAs. Clinical features of 11 patients, including 6 of our own and 5 reported by others, in whom the fusion of AF10 and CALM was identified, are characterized by young age of the patients, mixed-lineage immunophenotype with coexpression of T-cell and myeloid antigens, frequent occurrence of a mediastinal mass, and poor clinical outcome.

Adolescent↗
PubMed1999

Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants.

Of 29 infants with acute myeloid leukemia (AML), 14 (48%) had various 11q23 translocations. MLL rearrangements were examined in 21 of the 29 patients, and 11 (52%) showed the rearrangements. 11q23 translocations and/or MLL rearrangements were found in 17 (58%) of the 29 patients. While all but one of the 17 patients with 11q23/MLL rearrangements had M4 or M5 type of the FAB classification, the 12 patients without such rearrangements had various FAB types, including M2, M4, M4EO, M6 and M7. Of the 12 patients with other chromosome abnormalities or normal karyotypes, two had inv(16) ort(16;16), one had t(1;22)(p13;q13), and two had a novel translocation, t(7;12)(q32;p13). The breakpoint on 12p of the t(7;12) was assigned to intron 1 or the region just upstream of exon 1 of the TEL/ETV6 gene by fluorescence in situ hybridization. The event-free survival at 5 years for the 17 patients with 11q23/MLL rearrangements was 42.2%, and that for the 12 patients without such rearrangements was 31.3% (P = 0.5544). 11q231MLL rearrangements have been frequently reported and a poor prognosis in infant acute lymphoblastic leukemia implied. Our study showed that while 11q23/MLL rearrangements were also common in infant AML, AML infants with such rearrangements had a clinical outcome similar to that of AML infants without such rearrangements.

Acute Disease↗
PubMed1998

Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies.

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.

Acute Disease↗
PubMed1998

Amplification of the TCL1 flanking region at 14q32.1 with no TCL1 gene transcription in a patient with peripheral T cell lymphoma.

Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma (PTL) have not been well defined, except for those in adult T cell leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in tumor tissues from 20 patients with PTL including three with 14q32 translocations by two color fluorescent in situ hybridization (FISH) using two cosmid probes flanking the TCL1 gene. The two cosmid signals were separated in none of them, but much increased in number in one tumor without 14q32 translocation, indicating that the TCL1 genomic region was amplified in this tumor. Reverse transcription-polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript in the tumor. These findings suggest that an oncogene other than TCL1 may be located in 14q32.1, and its amplification may be involved in the neoplastic process of PTL.

Aged↗
PubMed1997

Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.

16;21 translocation is a recurrent primary abnormality in acute myeloid leukemia (AML). The genes involved in this translocation are ERG on chromosome 21 and TLS/FUS on chromosome 16. The rearrangement of the two chromosomes forms the TLS/FUS-ERG fusion gene and produces a consistent chimeric transcript on the der (21) chromosome. In this study, we analyzed the clinical characteristics of 19 patients with t(16;21)-AML, including 2 patients who evolved from myelodysplastic syndrome, and detected the chimeric transcripts of the TLS/FUS-ERG fusion gene in the patients during various clinical stages by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We found that the patients with t(16;21) are characterized by a relatively younger age (median age, 22 years old), involvement of various subtypes of French-American-British classification and a poor prognosis: 18 of the 19 patients died of the disease (median survival was 16 months). Four types of TLS/FUS-ERG chimeric transcripts including a novel type were noted in the RT-PCR analysis. The novel transcript contained an additional 138 nucleotides consisting of TLS/FUS exon 8 and ERG exons 7 and 8 and had an in-frame fusion. These chimeric transcripts were consistently detectable in the samples obtained not only at diagnosis and relapse but also in short and long complete remission, suggesting that t(16;21)-AML is resistant to conventional chemotherapy. Thus, we recommend that t(16;21) should be monitored by RT-PCR even in clinical remission and the patients should be treated by other more powerful modality like stem-cell transplantation in the first remission.

Acute Disease↗
PubMed1997

Minimal residual disease in acute monocytic leukemia patient with trisomy 11 and partial tandem duplication of MLL.

We studied MLL rearrangements in five patients with myeloid hematologic malignancies with trisomy 11. Two had acute monocytic leukemia (AMoL), one had chronic myelomonocytic leukemia, one had refractory anemia, and the other had juvenile chronic myelogenous leukemia. Only one patient, a 15-year-old boy with AMoL and simple trisomy 11, showed rearrangement of MLL. He did not respond to chemotherapy, and successfully underwent bone marrow transplantation, but suffered a relapse 22 months later. Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing analyses of bone marrow cells revealed a tandem duplication of MLL, and his relapse was predictable by sequential RT-PCR studies before it was clinically evident. Of 16 acute myeloid leukemia patients with trisomy 11 and rearrangement of MLL reported, our patient was the youngest in age and the only one with AMoL.

Adolescent↗
PubMed1997

Hematologic malignancies with the t(10;11) (p13;q21) have the same molecular event and a variety of morphologic or immunologic phenotypes.

Previous studies described the t(10;11)(p13-14;q14-21) as a recurring translocation associated with T-cell acute lymphoblastic leukemia (ALL). This translocation has also been reported in monocytic leukemia or ALL with a very early pre-B phenotype. However, whether these cytogenetically similar translocations involve the same molecular breakpoint is unknown. Using fluorescence in situ hybridization (FISH) with a series of probes on 11q, we mapped the 11q breakpoint of the U937 cell line, which was derived from a patient with diffuse histiocytic lymphoma and was shown by FISH to have the t(10;11)(p13-14;q14-21). Subsequently, we identified a yeast artificial chromosome (YAC) clone, y960g8, that included the breakpoint on 11q. From this YAC, we isolated a PI clone, P91B1, that was split by the 10;11 translocation. We studied four patients with a t(10;11), one of whom had acute monocytic leukemia (AMoL), one had acute lymphoblastic leukemia (ALL), one had lymphoblastic lymphoma (LBL), and one had granulocytic sarcoma, by using FISH with y960g8 and P91B1. Y960g8 and P91B1 were split by the translocation in each patient. We showed that P91B1 included a recently identified gene, CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), and that AF10 was also rearranged in each patient by FISH when we used y807b3, which contains the AF10 gene. These findings indicate that hematologic malignant diseases with fusion of AF10 and CALM show various morphologic and immunologic phenotypes, suggesting that this fusion occurs in multipotential or very early precursor cells.

Adult↗
PubMed1997

EWS-ERG fusion transcript produced by chromosomal insertion in a Ewing sarcoma.

The EWS gene is fused in Ewing sarcoma-like tumors by a chromosomal translocation to one of the four ETS-family genes: FLI1, ERG, ETV1, and E1AF. The orientation of EWS and FLI1 on chromosomes 22 and 11, respectively, is 5' centromeric and 3' telomeric, whereas that of ERG on chromosome 21 is the reverse. Although 10% of Ewing-family tumors express the EWS-ERG fusion transcript, there have been no reports on tumors with t(21;22)(q22;q12) identified by banding cytogenetics. We found the karyotype 50, XY, +8, +8, +12, +mar in all metaphase cells from a tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis performed on the tumor and direct sequencing of the products identified the EWS-ERG fusion transcript. Subsequent two-color fluorescence in situ hybridization (FISH) analysis with EWS and ERG clones showed the fused signals on the der(21) chromosome, but no ERG signals on the chromosome 22 homologs. Thus, our RT-PCR and FISH analyses indicated that the chromosome 22 fragment containing the 5' portion of EWS had been inverted and inserted into chromosome 21 and had fused to the 3' portion of ERG. This subtle chromosome aberration could not be identified by routine cytogenetics. A chromosomal inversion/insertion has also been described in acute leukemia with the MLL-AF10 fusion gene, and this may be a common pathway for producing fusion of reverse-oriented genes in leukemias and solid tumors.

Bone Neoplasms↗
PubMed1997

Inversion of chromosome 11 inv(11)(p15q22), as a recurring chromosomal aberration associated with de novo and secondary myeloid malignancies: identification of a P1 clone spanning the 11q22 breakpoint.

We studied four patients with inv(11)(p15q22) associated with malignant myeloid diseases by using fluorescence in situ hybridization (FISH) with phage and cosmid probes mapped and ordered on 11q22-24. Two of the four patients had non-Hodgkin's lymphoma or acute lymphoblastic leukemia as the primary malignancy and had received cytotoxic chemotherapy, including topoisomerase II inhibitors. The other two had de novo acute myeloid leukemia or myelodysplastic syndrome. FISH analysis showed that all 11q breakpoints were located centromeric to the MLL gene and between cosmids CN2900 and CN1323. We identified a yeast artificial chromosome (YAC) clone that spanned the inv(11) breakpoints on 11q. From this YAC, we identified a P1 clone, which included the breakpoints in at least three of the four patients. It is highly likely that the same gene on the P1 clone is rearranged in leukemic cells of each patient. This gene may be one of the targets for topoisomerase II inhibitors.

Adolescent↗
PubMed1997

Novel MLL-CBP fusion transcript in therapy-related chronic myelomonocytic leukemia with a t(11;16)(q23;p13) chromosome translocation.

CBP, which is located on 16p13 and encodes a transcriptional adaptor/coactivator protein, has been shown to fuse by the t(8;16)(p11;p13) translocation to MOZ on 8p11 in acute myeloid leukemia. We found a t(11;16)(q23;p13) in a child with therapy-related chronic myelomonocytic leukemia. Subsequent reverse transcriptase-polymerase chain reaction and direct sequencing analyses revealed the MLL-CBP fusion transcript in CMML cells. Because 11q23 translocations involving MLL and t(8;16) involving MOZ and CBP have been reported in therapy-related leukemias, both the MLL and CBP genes may be targets for topoisomerase II inhibitors. Accordingly, we believe that most t(11;16)-associated leukemias may develop in patients who have been treated with cytotoxic chemotherapy for primary malignant diseases.

Antineoplastic Combined Chemotherapy Protocols↗