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S Sadamura

Publications and source records attributed to S Sadamura.

8 recordsLinked to original sources

Analysis of clonality at the level of progenitors in chronic myelogenous leukaemia using the polymerase chain reaction.

The Philadelphia (Ph1) chromosome is a specific structural abnormality in which the abl oncogene is activated due to the formation of the novel chimeric gene, bcr/abl. To investigate the clinicopathological role of bcr/abl in Ph1-positive chronic myelogenous leukaemia (CML), we studied the clonal origin of haematopoietic progenitors by detecting bcr/abl mRNA in a single haematopoietic colony using the polymerase chain reaction (PCR). Nine patients with CML were examined. In 5 chronic phase patients, all granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitor-derived colonies were positive for bcr/abl mRNA. Colonies in which the transcripts were not detectable were observed in 4 patients. These 4 patients included one patient with a normal karyotype and without splenomegaly, a patient with cyclic oscillation of her white blood cell level, a patient treated with busulfan and interferon-alpha (INF-alpha), and a patient relapsing after allogenic bone marrow transplantation (BMT). Our observations indicate that detection of Ph1-positive clones by PCR may be used to evaluate clinical stages and the effects of treatment in CML.

Adolescent

Anemia and neutropenia in a case of copper deficiency: role of copper in normal hematopoiesis.

We present a patient who developed severe anemia and neutropenia after receiving parenteral nutrition for 2.5 years. The serum levels of copper and ceruloplasmin were low, and the bone marrow showed the presence of ringed sideroblasts and vacuolated immature cells. The administration of copper chloride by bolus injection led to a rapid improvement in anemia and neutropenia. The number of progenitor cells (colony-forming unit-granulocyte-macrophage and erythrocyte) present before the copper supplementation was well preserved. It is therefore suggested that copper enzymes play an important role in the maturation of hematopoietic cells.

Aged

Differences in tyrosine phosphorylated proteins between cells expressing P210bcr/abl and P190bcr/abl.

We analysed differences between the populations of tyrosine phosphorylated proteins in two cell lines, K-562 and MR-87, which express two different bcr-abl fusion gene products, using both immunoprecipitation and Western blotting with an anti-phosphotyrosine antibody. K-562 cells preferentially expressed P210bcr/abl (P210), while MR-87 expressed P190bcr/abl (P190). Tyrosine phosphorylated proteins with a molecular mass of 150 kDa (p150) and 115 kDa (p110) were found in both K-562 and MR-87. A 36 kDa protein (p36) was tyrosine phosphorylated in vivo only in K-562 cells, while proteins with a molecular mass of 140 kDa (p140) and 62 kDa (p62) were found only in MR-87 cells. Moreover, several proteins in the detergent-insoluble cell fraction were differently tyrosine phosphorylated in vitro in K-562 and MR-87 lysates. These results suggest that P210 and P190 may have different substrates, and thus, different signal transduction pathways for cell proliferation, although the differential association of such cellular proteins with the two bcr/abl products remains to be clarified.

Fusion Proteins, bcr-abl

[CD7 (+) stem cell leukemia presenting different phenotypes in lymph node and bone marrow].

A 27-year-old male with systemic lymphadenopathy was diagnosed as lymphoblastic-type lymphoma by inguinal lymph node biopsy in September, 1990. Bone marrow at the initial diagnosis contained 55.4% lymphoblasts with a phenotype of peroxidase (-), CD7 (+), CD4 (-), CD8 (-). Lymphadenopathy and lymphoblasts in bone marrow disappeared after MACOP-B therapy. In December, 1990, however, the patient again noticed swelling of cervical lymph nodes. At this time, the bone marrow contained 36.4% myeloblasts with a peroxidase (+), CD7 (+), CD13 (+), CD33 (+) phenotype. Cytogenetic and genetic study revealed that the lymphoblasts at the initial diagnosis and the myeloblasts at relapse shared an common abnormal karyotype, 11p-, and the same rearranged band of T-cell receptor delta, gamma, beta genes, suggesting that these two blasts originated from the same clone. The blasts obtained from the cervical lymph node at relapse were still negative for peroxidase, in contrast to the blasts from bone marrow. These findings suggest that this leukemia originated from a stem cell and differentiated along multilineage pathways.

Adult

[Two cases of acute promyelocytic leukemia in pregnancy and the effect of anthracyclines on fetal development].

Two patients with acute promyelocytic leukemia (APL) in 2nd and 3rd trimester of pregnancy are reported on. Case 1: 38-year-old female consulted our hospital because of bleeding tendency and pancytopenia in April, 1988. She was diagnosed as having APL with disseminated intravascular coagulopathy (DIC) and was found to be in the 14th week of gestation. Combined chemotherapy (BHAC-DMP) including the total dose (440 mg) of daunorubicin (DNR) resulted in intrauterine fetal death at 19 weeks of gestation. The fetus was severely anemic and the bone marrow was hypoplastic. Case 2: A 27-year-old female was diagnosed as having APL with DIC at 29 weeks of gestation. BHAC-DMP including 440 mg DNR achieved complete remission. At 35 weeks of gestation, she delivered a normal infant by Caesarean section. The child had normal hematological findings and showed normal growth. Both cases developed APL accompanied by DIC during pregnancy and were treated with a similar regimen including high dose of anthracyclines. Case 2 treated in the late period of gestation delivered a normal infant, while fetal death resulted in case 1, treated in the early period of gestation. We reviewed the literature regarding chemotherapy using anthracyclines during pregnancy.

Adult

P190-type bcr/abl expressed in myeloid colonies in a patient with Ph1-positive acute lymphoblastic leukemia.

In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph1-positive ALL, using the polymerase chain reaction (PCR). Seven out of 58 colonies examined expressed P190-type bcr/abl. Five out of seven colonies were granulocyte/macrophage (GM) colonies and two were erythroid colonies. The cell lineages of these colonies were confirmed by testing for the expressions of the myeloperoxidase (MPO) gene in the GM colonies and the beta-globin gene in the erythroid colonies. These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P190-type bcr/abl fusion gene permits stem cell differentiation leading to Ph1-positive ALL.

Adult

[A high serum level of interleukin-6 in a patient with aggressive multiple myeloma].

A 58-year-old female was admitted to our hospital because of anemia in March 1987. Monoclonal protein (IgA, kappa) was detected and a diagnosis of multiple myeloma was made. Partial remission was obtained after VAD therapy with alpha-interferon. In December 1989, she was readmitted because of a pathological fracture of the left humerus. A white blood cell count was 4400/microliters with 30% myeloma cells and the urine protein (Bence Jones protein) was 26 g/day. Systemic chemotherapy was not effective. She developed pleural and pericardial effusions, bone mass, disturbance of consciousness and died of respiratory failure only 3 months after readmission. The pleural and pericardial fluids contained many myeloma cells. c-myc gene rearrangement was detected in myeloma cells obtained from the pleural fluid using c-myc exon1 and exon2 probes. The levels of interleukin-6 (IL-6) measured by ELISA was 107.4 pg/ml in serum, 56.2 pg/ml in pleural fluid and 780.0 pg/ml in pericardial fluid. Because of the lack of any overt infectious focus, the level of IL-6 appears to have been related to aggressive proliferation of myeloma cells. It was of interest that C-reactive protein, induced by IL-6, was a good marker reflecting disease activity.

Antineoplastic Combined Chemotherapy Protocols

[Intestinal T-cell lymphoma (so-called malignant histiocytosis of the intestine) complicated by multiple perforations].

We describe a case of intestinal T-cell lymphoma which was histologically diagnosed of malignant histiocytosis of the intestine. A 47-year-old man was admitted to our hospital because of fever and generalized lymphadenopathy. Mild anemia, leukocytosis, positive CRP and a high level of LDH were noted. Pathological finding of the lymph node was compatible with dermatopathic lymphadenopathy with a slight increase in atypical lymphoid cells. At the 14th day after admission, he suffered from abdominal pain and was diagnosed as having perforative peritonitis. In laparotomy, the infiltration of histiocyte-like atypical cells were found around a site of small perforation of the terminal ileum. The findings were compatible with that of malignant histiocytosis of the intestine (MHI). He had recurrent perforations of the small intestine and died of peritonitis and sepsis at the 42nd day. Southern blot analysis of the biopsied lymph node showed TCR-beta gene rearrangement. Some patients diagnosed clinically and pathologically as having MHI may have a T-cell lymphoma like our case.

Histiocytic Sarcoma