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H Kiyoi

Publications and source records attributed to H Kiyoi.

63 records · Page 4Linked to original sources
PubMed1993

Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia.

We have screened mutations of the N-ras gene at codons 12, 13, and 61 in leukemia cells obtained from 100 patients with acute myeloid leukemia (AML), and found mutated N-ras alleles in 9 patients. We further analyzed the polyclonality of multiple N-ras gene mutations in 4 AML patients. One patient, who had the monoclonal karyotype, t(11;17), had two types of double missense mutations at codons 13 and 61 in the same allele. Each of the remaining three patients, one of whom had t(15;17) with a monoclonal rearrangement of the retinoic acid receptor alpha and PML genes, carried two missense mutations in a relatively small population of leukemia cells. We have demonstrated that multiple clonality of the N-ras gene is occasionally observed in leukemia with a monoclonal karyotype. These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia.

Acute Disease↗
PubMed1992

Effective treatment of adult T cell leukemia/lymphoma with a novel oral antitumor agent, MST-16.

Adult T cell leukemia/lymphoma (ATLL) induced by human T cell leukemia virus I is resistant to conventional therapy. Six patients with ATLL were treated with a new antitumor agent, MST-16, which is a derivative of bis(2,6-dioxopiperazine). Two patients achieved complete remission, lasting 12 months and more than 8 months, and 2 others partial remission, lasting 2 months and 6 weeks, respectively. The major toxicity was myelosuppression. Other toxicities were not severe and were well tolerable. Orally administered MST-16 is a promising agent for the treatment of ATLL.

Administration, Oral↗
PubMed1992

Characterization of the immunoglobulin heavy chain complementarity determining region (CDR)-III sequences from human B cell precursor acute lymphoblastic leukemia cells.

Sequence analysis of the immunoglobulin heavy chain complementarity determining region (CDR)-III of B-lineage cells at various stages has provided important insights concerning B cell maturation and selection. Knowledge of human CDR-III sequences has been relatively limited compared with that of the murine system. We analyzed the CDR-III sequences of B cell precursor acute lymphoblastic leukemia (pre-B ALL) cells in 23 newly diagnosed and 10 relapsed patients, in order to elucidate the organization of CDR-III in B cell precursors. We found a very low frequency of somatic mutations in D and JH regions, preferential use of DLR, DXP, DHQ52, and DN elements, and of 3' side JH segments, and no predominant usage of D coding frames. Unusual joinings such as VH-D-D-JH and VH-JH were observed in three, and one sequences, respectively. We compared the CDR-III sequences derived from 10 patients between diagnosis and relapse. Two of them had three spots of mutated nucleotides at relapse, all of which were found in the N region near the D segments. Our data showed the possibility of somatic mutation at relapse, in addition to developmentally regulated rearrangement of the immunoglobulin gene at the stage of B cell precursors.

Adolescent↗
PubMed1991

Disappearance of minimal residual lymphoblastic leukemia cells 6 months after allogeneic bone marrow transplantation without GVHD.

The recent development of the polymerase chain reaction (PCR) has enabled us to determine the hypervariable sequence of immunoglobulin heavy chain known as complementarity determining region (CDR)-III. We amplified the leukemia-specific CDR-III from common acute lymphoblastic leukemia (cALL) cells using the PCR and determined its sequence. To detect minimal residual leukemia (MRL) cells, a second round PCR was performed with clone-specific primers corresponding to 5' and 3' ends of CDR-III to detect MRL cells. A million-fold diluted leukemia cells were clearly detected. Using stepwise diluted materials, the number of residual cells was semiquantitatively estimated. In one patient with cALL, induction chemotherapy resulted in a hematologically complete remission with only a 2-log reduction of the leukemia cells. MRL cells at a level of 10(-6) were also detected within 1 month after bone marrow transplantation (BMT), but leukemia cells were not detectable 6 months after BMT.

Adult↗
PubMedDate not supplied

Prognostic significance of TEL/AML1 fusion transcript in childhood B-precursor acute lymphoblastic leukemia.

PURPOSE: A retrospective study was conducted to investigate the prognostic significance of TEL/AML1 fusion resulting from a cryptic t(12;21) in Japanese patients with childhood B-precursor acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Leukemic samples from 144 children with newly diagnosed ALL (104 with CD10-positive B-precursor ALL, 11 with CD10-negative B-precursor ALL, 5 with B-ALL, and 24 with T-ALL) were analyzed by reverse-transcription polymerase chain reaction. RESULTS: The frequency of patients with TEL/AML1 was 16% (23 of 144) and all patients with TEL/AML1 also had CD10-positive B-precursor ALL. TEL/AML1 was not found in any samples from the patients with T-ALL, B-ALL, or CD10-negative B-precursor ALL. Among patients with CD10-positive B-precursor ALL, age, initial white blood cell count, and immunophenotype did not differ with TEL/AML1 positivity, although the patients were predominantly male (p < 0.01). Clinical outcomes of 94 patients treated with recent protocols were analyzed. Five of the 21 (23.8%) patients with TEL/AML1 relapsed and 4 of these relapsed > 24 months after diagnosis. Although the overall 5-year survival rate was better among patients with TEL/AML1 fusion transcript than among those without it (87.3 +/- 8.7% versus 75.9 +/- 5.8%, respectively), the 5-year disease-free survival (DFS) rates of patients with TEL/AML1 fusion transcript and those without it were similar (64.0 +/- 13.5% versus 69.1 +/- 6.3%, respectively). However, for 57 patients treated with the latest intensive protocol, the 4-year DFS rate was much higher for the patients with TEL/AML1 fusion transcript than for those without it (100.0% v.s. 69.6 +/- 8.4%, respectively, p = 0.1472). CONCLUSIONS: This study confirmed that TEL/AML1 gene fusion is the most common genetic event in pediatric ALL in Japan and is restricted to CD10-positive B-precursor ALL. Moreover, it was associated with an improved survival rate among patients treated with intensive therapy. Therefore, these data suggest that the patients with TEL/AML1 may not necessarily be candidates for less aggressive treatment.

Adolescent↗