Biomedical subjects

S Sadamura

Publications and source records attributed to S Sadamura.

17 recordsLinked to original sources

PubMed1996

Expression of EVI1 and the Retinoblastoma genes in acute myelogenous leukemia with t(3;13)(q26;q13-14).

The EVI1 DNA-binding protein gene on chromosome 3q26 has been reported to be activated in some leukemia cells with alterations in 3q26. We present an acute myelogenous leukemia (AML) patient with a rare chromosomal translocation, t(3;13)(q26.2;q13-14). By reverse transcription-polymerase chain reaction, we detected active transcription of the EVI1 gene in the patient's leukemia cells. The retinoblastoma susceptibility (Rb) gene, a tumor-suppressor gene, is located at chromosome 13ql4 and is within the other translocation breakpoint in this patient. The expression of the Rb gene product was found to be substantially decreased in the patient's leukemia cells by Western blotting. Southern blot analysis, however, revealed no gross abnormalities of the Rb gene. Although it is unlikely that the Rb gene is directly involved in this translocation, the loss of the Rb gene product combined with the activation of the EVI1 gene may have led to the development of leukemia.

Asian People↗

PubMed1996

Acute leukemias expressing p210-and p 190-type bcr/abl mRNAs: report of two cases and review of the literature.

We report two patients with acute leukemias who expressed two types of bcr/abl mRNA. The first case was an 8-year-old boy with acute mixed leukemia in whom the Ph1 chromosome and p210/p190 types of bcr/abl mRNAs were detected at diagnosis. The second case was a 39-year-old male with acute nonlymphocytic leukemia transformed from myelodysplastic syndrome (refractory anemia with excess of blasts). In the latter case, the p210-type mRNA appeared after leukemic transformation, and the p190-type transcript was detected only during the late stage when the Ph1 chromosome was first observed. The leukemias in these two patients were aggressive in their clinical courses. We conclude that the dual expression of p210 and p190 types of bcr/abl is a factor indicating a poor prognosis, and that, in some patients, p190-type bcr/abl may contribute to disease progression.

Acute Disease↗

PubMed1995

Detection of minimal residual disease by reverse transcriptase polymerase chain reaction for the PML/RAR alpha fusion mRNA: a study in patients with acute promyelocytic leukemia following peripheral stem cell transplantation.

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by the presence of a PML/RAR alpha fusion gene resulting from t(15;17). Peripheral stem cell transplantation (PSCT) has been used to treat patients with AML. To assess the presence of minimal residual disease (MRD) and the contamination of leukemic cells in peripheral stem cells (PSCs), we examined six patients with APL who were undergoing PSCT, using reverse transcriptase polymerase chain reaction analysis to detect the mRNA of the PML/RAR alpha fusion gene. The fusion gene was expressed in the bone marrow cells during the early phase of a complete remission and in some of the PSCs. Detection of the fusion gene can be useful in monitoring for leukemic cell contamination of PSCs and for predicting a relapse of APL.

Base Sequence↗

PubMed1994

Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage.

We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was not detected until the late stage of ANLL transformation, 14 months after the transformation following a 3-month history of refractory anaemia with excess of blasts. The cells with and without the Ph1 chromosome had a common abnormal chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore, the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic analysis. These evidences support a multistep pathogenesis of leukaemias, and the products of bcr/abl fusion gene may influence the course of disease.

Adult↗

PubMed1994

Detection of bcr/abl mRNA in stained bone marrow smears.

We describe the polymerase chain reaction (PCR) method using stained bone marrow smears as sources of RNA. The amount of extractable RNA decreased during the process of making and staining bone marrow smears. The sensitivity of the reverse transcriptase-based polymerase chain reaction (RT-PCR) method for detecting target mRNA-positive cells in 5 x 10(5) suspended cells and stained bone marrow smears were 1:10(5) and 1:5000, when we used K562 cells. The bone marrow smears of 21 patients with chronic myelogenous leukemia (CML) were examined using this method. We extracted RNA from stained specimens stored at room temperature for 5-14 years. Twelve of 21 (57%) smears showed positive results for bcr/abl. The carrier RNA improved the recovery when added at the step of RNA extraction. These data indicate that mRNA is present in stained bone marrow smears for at least 14 years and that the sensitivity of RT-PCR is adequate for molecular analysis.

Base Sequence↗

PubMed1993

CD7+ stem cell leukemia/lymphoma. Features of a subgroup without circulating blast cells.

Recent advances in immunology have clarified the cellular origin of hematopoietic neoplasms. Blast cells with a CD7+ CD4- CD8- phenotype are demonstrated to originate from malignant pluripotent hematopoietic stem cells. In this article, the authors describe three rare cases, designated as a lymphoma type of CD7+ stem cell leukemia/lymphoma, with clinical features described below. All three patients were admitted with non-Hodgkin lymphoma with a 2-month to 4-month history of lymphadenopathy. Histologic examination of lymph nodes showed lymphoblastic lymphoma (LBL) in all patients. Bone marrow blast cells had an immunophenotype consistent with CD7+ CD4- CD8- acute leukemia, although abnormal cells were not observed in the peripheral blood during the course of the disease. One patient had a recurrence in the bone marrow, with myeloperoxidase-positive blast cells expressing myeloid differentiation antigens. Chromosomal analysis detected a common abnormal karyotype initially and at relapse. Furthermore, the same T-cell receptor gene rearrangement was found initially and at relapse, suggesting that these blast cells originated from the same pluripotent leukemic clone. Additional studies on more patients are required to determine the clinical significance of this group, including the difference from CD7+ stem cell leukemia/lymphoma with circulating blast cells (leukemic type) or LBL.

Acute Disease↗

PubMed1993

Double t(1;7)(p36;p11) in a megakaryocytic crisis of chronic myelogenous leukemia with variant t(5;9;22).

A 56-year-old man with chronic myelogenous leukemia (CML) who presented with a variant Ph chromosome, t(5;9;22)(q13;q34;q11), developed a unique additional chromosomal change of a double reciprocal t(1;7)(p36;p11) during the accelerated phase. A minor clone that had two copies of 1p+ and a copy of 7p- with a normal chromosome 7 was observed simultaneously. The patient underwent a megakaryocytic crisis. Surface marker of the blasts was positive for CD13, CD33, HLA-DR, CD41a, and CD42b, and negative for CD14 and lymphoid markers. Sequential chromosome analysis suggests that the double t(1;7) was caused by a multistep event consisting of duplication of both derivative chromosomes accompanied by loss of normal chromosomes 1 and 7. This may be the first report of a double reciprocal chromosomal translocation in a hematopoietic neoplasm.

Chromosome Banding↗

PubMed1993

Recurrent appearance of 14q+ chromosome associated with lymphoid crisis of Ph-positive chronic myelogenous leukemia.

The 14q+ chromosomal anomaly commonly found in cases of lymphoid neoplasm recurrently occurred during the lymphoid crisis of a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). At presentation lymphoblasts, with pre-B phenotype increased, and both the Ph and 14q+ were found in the same metaphases. After treatment with vincristine and prednisolone, the patient entered into the chronic phase, and only a Ph was detected in 100% of the cells examined. The 14q+ reappeared at the recurrence of the lymphoid crisis, and then disappeared in the second chronic phase. The BCR/ABL mRNA, which is specific for CML, was detected in the blastic cells by a method using reverse transcriptase and polymerase chain reaction. The rearrangement of the immunoglobulin heavy chain gene (JH gene) was also detected in the blastic cells. These results suggest that the 14q+ was closely associated with the lymphoid crisis of the CML patient.

Chromosome Aberrations↗

PubMed1993

PML/RAR alpha fusion gene is expressed in both granuloid/macrophage and erythroid colonies in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia (APL) associated with a t(15;17) translocation generates a PML/RAR alpha chimaeric gene which is transcribed as a fusion PML/RAR alpha mRNA. To clarify the pathophysiologic role of PML/RAR alpha in APL patients, we examined the expression of PML/RAR alpha in haemopoietic colonies in five patients with APL by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. By the two-step RT-PCR method, we demonstrated that PML/RAR alpha positive clones were present in progenitor cells including both CFU-GM and BFU-E in two cases. This result suggests that the translocation of PML/RAR alpha occurred in a pluripotent stem cell in some APL patients. In four patients we detected two amplified cDNA fragments of 780 and 640 bp which presumably arose by alternative splicing of the PML gene. Interestingly, of CFU-GM and BFU-E colonies examined in four patients, there were three different types of colonies: those expressing only the 780 bp fragment, those expressing only the 640 bp fragment, and those expressing both fragments. This suggests that alternative splicing was clonally determined in each colony. We describe a useful RT-PCR technique for the study of gene expression in a limited number of haemopoietic precursor cells.

Adult↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

[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↗

PubMed1992

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↗

PubMed1991

[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↗

PubMed1991

[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↗