ABSTRACT
The unbalanced translocation, der(1;7)(q10;p10), is one of the characteristic cytogenetic abnormalities found in myelodysplastic syndromes (MDS) and other myeloid neoplasms. Although described frequently with very poor clinical outcome and possible relationship with monosomy 7 or 7q- (-7/7q-), this recurrent cytogenetic abnormality has not been explored fully. Here we analyzed retrospectively 77 cases with der(1;7)(q10;p10) in terms of their clinical and cytogenetic features, comparing with other 46 adult -7/7q- cases without der(1;7)(q10;p10). In contrast with other -7/7q- cases, where the abnormality tends to be found in one or more partial karyotypes, der(1;7)(q10;p10) represents the abnormality common to all the abnormal clones and usually appears as a sole chromosomal abnormality during the entire clinical courses, or if not, is accompanied only by a limited number and variety of additional abnormalities, mostly trisomy 8 and/or loss of 20q. der(1;7)(q10;p10)-positive MDS cases showed lower blast counts (P<0.0001) and higher hemoglobin concentrations (P<0.0075) at diagnosis and slower progression to acute myeloid leukemia (P=0.0043) than other -7/7q- cases. der(1;7)(q10;p10) cases showed significantly better clinical outcome than other -7/7q cases (P<0.0001). In conclusion, der(1;7)(q10;p10) defines a discrete entity among myeloid neoplasms, showing unique clinical and cytogenetic characteristics.
Subject(s)
Chromosome Aberrations , Leukemia, Myeloid, Acute/genetics , Myelodysplastic Syndromes/genetics , Myeloproliferative Disorders/genetics , Translocation, Genetic , Adolescent , Adult , Aged , Aged, 80 and over , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 7 , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Myelodysplastic Syndromes/pathology , Myeloproliferative Disorders/pathology , Retrospective StudiesABSTRACT
We investigated the polymorphic CAG-repeat distribution and the X-inactivation status of the human androgen receptor (HUMARA) gene in 58 female Japanese volunteers. Polymerase chain reaction amplification was performed using a fluorescent-dye-labeled primer under conditions specific for GC-rich targets, and fragments were analyzed. To estimate the length of these fragments, FAM-labeled (blue fluorescent) products were simultaneously compared with ROM-labeled size markers (red) that were created by sequencing various HUMARA fragments. The number of polymorphic CAG repeats of HUMARA in 116 alleles from 58 female subjects ranged from 15 to 28. Of the 58 volunteers, 51 (88.0%) were heterozygous. In 96% of the heterozygous female subjects, the allelic differences were no greater than 6 repeats. X-chromosome inactivation was calculated as the ratio of the area of the smaller peak to the sum of the areas of the smaller and larger peaks. The average ratio was 0.38 (range, 0.09-0.50). Preferential use of 1 allele, by more than 75% (ratio. <0.25). was observed in 5 volunteers (10.9%). The clonal nature of a patient with chronic myelogenous leukemia was easily identified. This method is sensitive enough to discriminate a difference of 1 triplet repeat.
Subject(s)
Dosage Compensation, Genetic , Receptors, Androgen/genetics , Trinucleotide Repeats/genetics , Clonal Deletion , Clone Cells , Female , Fluorescent Dyes , GC Rich Sequence , Heterozygote , Humans , Japan , Mosaicism/genetics , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/standards , Polymorphism, Genetic/genetics , Sensitivity and SpecificityABSTRACT
BACKGROUND: The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out. STUDY DESIGN AND METHODS: E variants from healthy Japanese blood donors were screened by serologic analysis using E MoAbs. Fifteen E variant samples were divided into three types--EFM, EKH, and EKK-on the basis of patterns of reactivity with five distinct E antibodies. The entire coding region of the Rh cDNAs from the E variant samples was analyzed by sequencing. RESULTS: Although the Rh cDNA sequences of the three types were different from each other, those of the EFM-type variants (RHEFM) had a partial DNA exchange in exon 5 between the RHCE and RHD genes, generating an RHcE variant (Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a point mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg154Thr substitution in the third external loop of the RhcE peptide. The EKK-type variant (RHEKK) carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene. The RHD gene of a person possessing an E variant of the EKK type was also a hybrid gene, D-cE(2-3)-D or cE(1-3)-D (RHDKK). The E variants of types EKH and EKK showed weak c antigenicity. CONCLUSION: In serologic screening of 140,723 Japanese blood donors, 15 were found to possess E variants (0.011%). A new RHCE variant, RHEKH, was identified. On the basis of the variants found in this study, the c antigenicity seemed to be determined not only by Pro-103 but also by the structure of the third extracellular loop or the amino acids contained in it.
Subject(s)
Asian People/genetics , Genetic Variation , Isoantigens/genetics , Rh-Hr Blood-Group System/genetics , Amino Acid Substitution , Base Sequence/genetics , Blood Donors , Glycoproteins/genetics , Humans , Isoantigens/immunology , Japan , Mass Screening , Protein Structure, Tertiary/genetics , Reference ValuesABSTRACT
The specificity of autoantibodies in autoimmune hemolytic anemia (AIHA) has been studied using the serological procedure and immunoprecipitation technique with rare phenotype red cells. We attempted to analyze specificity using recombinant rhesus (Rh) blood group and band3 antigens expressed on erythroleukemic cell lines, KU812E. The autoantibody eluates were isolated by the acid elution procedure from the red cells of 20 AIHA patients. The recombinant Rh antigens, RhD, cE, ce, CE, and chimera antigens CE-D and D-CE, were obtained by retroviral cDNA transduction into KU812E cells, and the cell line expressing the antigens was cloned. Band3 cDNA was also obtained and introduced into KU812E and cloned KU812 expressing RhcE. The reactivities of AIHA eluates with recombinant Rh and band3 antigens were studied by flow cytometry. Fifteen eluates reacted with at least one of the RhcE, ce, or CE antigens, and four eluates reacted with RhD. Seven eluates with strong Rh specificity were studied further using chimera antigen. Five eluates showed reduced or lost reactivity, although two eluates reacted identically with the chimera antigens as wild type. These results indicated that conformational epitopes constituted by RhD or CE specific exofacial peptide loops are important for autoantibodies in most cases. Seven eluates reacted with band3, five exclusively. The coexpression study of RhcE and band3 did not enhance the expression of either antigen nor the reactivity with patient eluates, indicating that association of Rh and band3 was not involved in the appearance of autoantigen.
Subject(s)
Anemia, Hemolytic, Autoimmune/blood , Anion Exchange Protein 1, Erythrocyte/immunology , Autoantibodies/immunology , Rh-Hr Blood-Group System/immunology , Anemia, Hemolytic, Autoimmune/immunology , Anion Exchange Protein 1, Erythrocyte/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/metabolism , Antibody Specificity , Antigen-Antibody Complex/analysis , Autoantibodies/blood , Autoantibodies/isolation & purification , Epitopes , Erythrocytes/chemistry , Erythrocytes/immunology , Flow Cytometry , Humans , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Recombinant Proteins/immunology , Transduction, Genetic , Tumor Cells, CulturedABSTRACT
We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.
Subject(s)
Amikacin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Cephalosporins/administration & dosage , Drug Therapy, Combination/administration & dosage , Hematologic Neoplasms/complications , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/etiology , Female , Humans , Immunocompromised Host , Male , Middle Aged , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/etiology , Sepsis/drug therapy , Sepsis/etiology , CefozopranABSTRACT
A 40-year-old man was diagnosed as having chronic myeloid leukemia (CML) in December 1990 and received busulfan and hydroxyurea. He developed myeloid blast crisis in February 1996. After DCMP combination chemotherapy, his disease reverted to chronic phase, but right hypochondrial pain developed and low-grade fever persisted. Abdominal CT scan revealed multiple low-density areas in the liver, suggestive of abscess formation. Grocott staining of a liver biopsy sample revealed granuloma and fungus. The patient was treated with intravenous amphotericin B (AMPH-B) without success. AMPH-B was then administered via a catheter placed in the portal vein on January 6, 1997, and an additional catheter placed in the hepatic artery on March 28. AMPH-B was administered through both catheters for more than two months, but later substituted by fluconazole because of renal impairment. On September 10, allogeneic bone marrow transplantation from the patient's HLA-identical brother was performed, despite persistence of the abnormal CT findings. Acute grade III GVHD developed, but there was no evidence of reactivation of the liver abscesses. This case demonstrates that a prior fungal liver abscess is not an absolute contraindication for BMT if prophylactic antifungal drugs are administered and careful observation is conducted.
Subject(s)
Blast Crisis , Bone Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Liver Abscess/drug therapy , Mycoses/drug therapy , Adult , Amphotericin B/administration & dosage , Antifungal Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluconazole/therapeutic use , Humans , Male , Transplantation, HomologousABSTRACT
We report a 67-year-old patient with coexistent tracheal non-Hodgkin's lymphoma and lung cancer the first case, to our knowledge, of this concomitant incidence in the literature. Chest radiography showed a mass in the right lung and pulmonary fibrosis. Biopsy of the unanticipated tracheal irregularity revealed non-Hodgkin's lymphoma, compatible with mucosa-associated lymphoid tissue lymphoma. After right upper lobectomy, chemotherapy for non-Hodgkin's lymphoma was conducted, but the patient died 11 months postoperatively of pulmonary fibrosis. Pulmonary fibrosis was suspected of having progressed from drug-induced pneumonitis caused by anticancer drugs. A common tumorigenetic factor may thus exist between tracheobronchial mucosa-associated lymphoid tissue lymphoma and lung cancer.
Subject(s)
Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, Non-Hodgkin/pathology , Neoplasms, Multiple Primary , Tracheal Neoplasms/pathology , Aged , Carcinoma, Squamous Cell/surgery , Humans , Lung Neoplasms/surgery , Lymphoma, B-Cell, Marginal Zone/surgery , Lymphoma, Non-Hodgkin/surgery , Male , Pulmonary Fibrosis/complications , Tracheal Neoplasms/surgeryABSTRACT
A 45-year-old man was diagnosed as having Ph1+ acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy. Allogeneic BMT from his HLA-identical sister was performed on June 11, 1997. Engraftment was relatively quick, but acute GVHD (grade I) developed. The patient was discharged on day 113. Seven months after BMT, in January 1998, exertional dyspnea developed gradually. Chest X-ray examination showed diffuse interstitial pneumonia, for which corticosteroid was started immediately. The symptoms and signs gradually improved. However, on the 20th hospital day (February 23), bilateral subcutaneous emphysema developed in the neck and supraclavicular region. Chest X-ray and CT examinations showed pneumomediastinum without pneumothorax. The pneumomediastinum and subcutaneous emphysema gradually subsided after 3 weeks of bed rest. Subcutaneous emphysema and pneumomediastinum are relatively rare complications of allogeneic BMT.
Subject(s)
Bone Marrow Transplantation/adverse effects , Mediastinal Emphysema/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Subcutaneous Emphysema/etiology , Humans , Male , Middle Aged , Transplantation, HomologousSubject(s)
Anemia, Hemolytic, Autoimmune , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/therapy , Anti-Inflammatory Agents/administration & dosage , Autoantibodies/blood , Autoantigens/blood , Coombs Test , Erythrocytes/immunology , Humans , Immunosuppressive Agents/therapeutic use , Prednisolone/administration & dosage , SplenectomyABSTRACT
The sialomucin CD34 is a useful marker for hematopoietic stem/progenitor cells. However, the role of CD34 remains poorly understood. Here we investigate the functions of CD34 and another sialomucin CD43 coexpressed on hematopoietic stem/progenitor cells. Stimulation of undifferentiated hematopoietic KG1a cells with anti-CD34 or anti-CD43 induced homotypic cytoadhesion, accompanied by formation of a long-lived cap of CD34 and CD43 respectively, which colocalized with F-actin. Stimulation with either antibody specifically increased tyrosine phosphorylation of the identical set of proteins of Lyn, Syk, pp60, pp69, and pp77 at the capping site. These events were similar to those observed in monocytic U937 cells ectopically expressing CD34. After stimulation of KG1a cells, coimmunoprecipitation of Lyn with pp69 and pp77 and of Syk with pp37 was detected in the membrane fraction. Blockade of antibody-induced cap formation by treatment with cytochalasin D leads to inhibition of tyrosine phosphorylation of Syk and pp77 and homotypic cytoadhesion. Moreover, normal human CD34(+) bone marrow cells showed cap formation of CD34 or CD43 after stimulation. These results suggest that crosslinking of either CD34 or CD43 activates the same signaling pathway for cytoadhesion through Lyn, Syk, and the novel tyrosine-phosphorylated proteins within hematopoiesis.
Subject(s)
Antigens, CD34/physiology , Antigens, CD , Enzyme Precursors/physiology , Hematopoietic Stem Cells/physiology , Protein-Tyrosine Kinases/physiology , Sialoglycoproteins/physiology , Signal Transduction/physiology , src-Family Kinases/physiology , Cell Adhesion/physiology , Hematopoietic Stem Cells/pathology , Humans , Intracellular Signaling Peptides and Proteins , Leukosialin , Receptor Aggregation/physiology , Syk Kinase , Tumor Cells, Cultured , U937 CellsABSTRACT
1q21 is frequently involved in different types of translocation in many types of cancers. Jumping translocation (JT) is an unbalanced translocation that comprises amplified chromosomal segments jumping to various telomeres. In this study, we identified a novel gene human JTB (Jumping Translocation Breakpoint) at 1q21, which fused with the telomeric repeats of acceptor telomeres in a case of JT. hJTB (human JTB) encodes a trans-membrane protein that is highly conserved among divergent eukaryotic species. JT results in a hJTB truncation, which potentially produces an hJTB product devoid of the trans-membrane domain. hJTB is located in a gene-rich region at 1q21, called EDC (Epidermal Differentiation Complex). This is the first report identifying the gene involved in unbalanced translocations at 1q21.
Subject(s)
Chromosomes, Human, Pair 1/genetics , Membrane Proteins/genetics , Neoplasm Proteins , Neoplasms/genetics , Translocation, Genetic , Amino Acid Sequence , Base Sequence , Cell Differentiation/genetics , Conserved Sequence , Epidermal Cells , Eukaryotic Cells , Female , Humans , Leukemia/genetics , Molecular Sequence Data , Myelodysplastic Syndromes/genetics , Ovarian Neoplasms/genetics , Sequence Homology, Amino AcidABSTRACT
Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.
Subject(s)
Leukemia, Neutrophilic, Chronic/diagnosis , Polycythemia Vera/diagnosis , Busulfan/therapeutic use , Humans , Hydroxyurea/therapeutic use , Leukemia, Neutrophilic, Chronic/drug therapy , Male , Middle Aged , Polycythemia Vera/drug therapyABSTRACT
We examined 159 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan. The subjects were divided in three groups; 90 patients with thrombotic thrombocytopenic purpura, 51 patients with verotoxin-induced hemolytic uremic syndrome, and 18 patients with drug-induced hemolytic uremic syndrome. Eighty-two percent of the patients with thrombotic thrombocytopenic purpura had associated neurological disorders and 78% of drug-induced hemolytic uremic syndrome associated with pulmonary edema. Renal insufficiency was noted in the 69% cases with both hemolytic uremic syndrome groups. Seventeen patients with thrombotic thrombocytopenic purpura had systemic lupus erythematosus and 6 were pregnant. Autoantibody were positive in 53% of thrombotic thrombocytopenic purpura. Seventy-seven percent of patients with thrombotic thrombocytopenic purpura received plasma exchange at 4,000 mL/day three times a week, 71% antithrombotic agents, and 78% steroid administration, respectively. However, 27% of the patients with hemolytic uremic syndrome were treated by hemodialysis in addition to antithrombotic agents. When drug-induced hemolytic uremic syndrome was diagnosed, the drug was immediately discontinued and the patients were treated with antiplatelet agents. Seventy-four percent of the patients with thrombotic thrombocytopenic purpura were alive at 26 weeks compared with 95% of those with hemolytic uremic syndrome. As thrombotic thrombocytopenic purpura had a high mortality rate in Japan, we should carry out early diagnosis and early treatment.
Subject(s)
Hemolytic-Uremic Syndrome/drug therapy , Purpura, Thrombotic Thrombocytopenic/drug therapy , Adolescent , Adult , Aged , Aspirin/administration & dosage , Bacterial Toxins , Child , Child, Preschool , Clinical Trials as Topic , Disease-Free Survival , Female , Fibrinolytic Agents/administration & dosage , Hemolytic-Uremic Syndrome/chemically induced , Heparin/administration & dosage , Humans , Infant , Infant, Newborn , Japan/epidemiology , Male , Methylprednisolone/administration & dosage , Middle Aged , Mitomycin/administration & dosage , Plasma Exchange , Platelet Aggregation Inhibitors/therapeutic use , Pregnancy , Recurrence , Renal Dialysis , Shiga Toxin 1 , Steroids/administration & dosage , Survival Rate , Treatment OutcomeABSTRACT
Rh blood group antigens are associated with non-glycosylated human erythrocyte membrane proteins encoded by two closely related genes, RHCE and RHD, and with a glycoprotein, a critical co-expressing factor encoded by the RH50 gene. The sequence analysis of RHCE transcripts has revealed that RhE/e and C/c serological phenotypes are associated with a nucleotide substitution in exon 5 and six substitutions in exons 1 and 2 of RHCE gene, respectively. Smythe et al. have shown that the full length transcript of RhcE gene expressed c and E antigens and the transcript of RhD gene expressed D and G antigens, using retroviral-mediated gene transduction into K562 cells. We performed an epitope analysis of Rh antigen by constructing retroviral gene coding six RH cDNAs, which contain RhcE, ce, CE and D cDNAs, and CE-D, D-CE chimera cDNAs. The cDNAs were introduced into KU812E cells and the expressed antigens were analyzed by flow cytometry. These studies revealed that the C/c and E/e associated substitutions actually participated in respective polymorphic epitopes. However, the C antigen was not detected on the KU812E cells introduced with CE cDNA, despite E antigen being expressed. The study with the chimera gene between CE and D cDNAs also indicated that the Rh epitopes were not constructed with short polymorphic exofacial peptide loops only but also with other peptide fragments and membrane components. Co-expression studies of Rh50 and RhD or cE gene in non-erythroid cells, 293, and expression studies of Rh50 in another erythroid cell, HEL, did not show any Rh antigens on the transduced cells, despite the Northern blot study showing both transcripts in the cells. It was suggested that at least a second co-expressing factor was needed to express RhCE or D antigens on the plasma membrane.
Subject(s)
Erythrocytes/immunology , Isoantigens/blood , Rh-Hr Blood-Group System/genetics , Transduction, Genetic , Cell Line , Humans , Rh-Hr Blood-Group System/immunologyABSTRACT
We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.
Subject(s)
Antigens, CD , Hypergammaglobulinemia/complications , Immunoblastic Lymphadenopathy/complications , Lymphoma, T-Cell/complications , Paraproteinemias/complications , Plasma Cells/pathology , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Aged , Antigens, Differentiation , Cell Division , Female , Flow Cytometry , Fluorescent Antibody Technique, Indirect , Humans , Hypergammaglobulinemia/immunology , Immunoblastic Lymphadenopathy/immunology , Lymphoma, T-Cell/immunology , Membrane Glycoproteins , NAD+ Nucleosidase , Paraproteinemias/immunology , Plasma Cells/immunologyABSTRACT
To evaluate the long-term effectiveness of interferon-alpha (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML) in chronic phase, we examined the updated outcomes of 159 patients who had been enrolled between 1988 and 1991 into a randomized trial comparing IFN-alpha with busulfan. At a median follow-up of 73 months, the median survival was 71 months in the IFN-alpha group and 55 months in the busulfan group (P=0.0563), and the median time of remaining in chronic phase was 58 months in the IFN-alpha group and 39 months in the busulfan group (P=0.4676). Landmark analysis showed a significant advantage in survival (P=0.009) and duration of chronic phase (P=0.0001) in patients with any cytogenetic response among the IFN-alpha group. About half patients were discontinued IFN-alpha administration in spite of cytogenetic response in this study. It appears that continuation of IFN-alpha might possibly confer a survival advantage. Pretreatment factors associated with cytogenetic response included high hemoglobin level, low percentage of peripheral basophils and low leukocyte counts. Multivariate analysis identified lower percentage of bone marrow basophilia (P=0.007) for survival advantage. If a group with a very good prognosis is predicted by a new prognostic model, it might be an option to wait for bone marrow transplantation.