Hematopathology and molecular hematology最新文献

{"title":"Adult acute leukemia: hand mirror cell variant.","authors":"A Wibowo,&nbsp;D Pankowsky,&nbsp;A Mikhael,&nbsp;T Wright,&nbsp;P E Steele,&nbsp;H Schumacher","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Two patients with numerous hand mirror cells in the bone marrow were investigated by morphologic, cytochemical, immunohistochemical, flow cytometric, cytogenetic, and gene rearrangement analysis. Both demonstrated a mixed immunophenotype with expression of myeloid and T-lymphoid features. Interestingly, both strongly expressed CD2 (adhesion molecule) and CD7. Review of the literature uncovered additional cases of acute mixed leukemia--hand mirror variant with strong expression of CD2, CD7, and CDIIb, suggesting a unique subset. Under normal physiologic conditions lymphoid cells and monocytes assume a hand mirror configuration when adhesion molecules (i.e., CD2, CDIIb) are triggered by their corresponding ligands. Evidently not all acute leukemias with surface adhesion molecules form hand mirrors, which suggests an additional stimulatory event. The presence of adhesion molecules on these activated cells is important to homing, trafficking, spread of the malignant cells, clinical course, prognosis, and treatment. Therefore all HMC cases require detailed analysis to ensure accurate diagnosis. In-depth evaluation of such cases should give new insights into clinical presentation, prognosis, and treatment of these unusual cases.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical study of Ulex europaeus agglutinin 1 (UEA-1) binding of megakaryocytes in bone marrow biopsy specimens: demonstration of heterogeneity in staining pattern reflecting the stages of differentiation.","authors":"S M Liu,&nbsp;C Y Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During differentiation, megakaryocytes undergo nuclear endoreplication, an increase in cell size, cytoplasmic granulation, and release of platelets. The changes in highly lobulated nuclei with varying degree of polyploidy and increasing cell size are easily recognized morphologically. However, the actual cytoplasmic changes are more difficult to perceive morphologically. With the peroxidase-antiperoxidase (PAP) method using UEA-1 as the binding protein to the alpha-L-fucose of glycoprotein synthesized by megakaryocytes, we observed significant variation in cytoplasmic staining of megakaryocytes in routinely processed bone marrow biopsy sections. A total of 3344 megakaryocytes in bone marrow sections from 10 patients with nonhematologic diseases and from 10 patients with idiopathic thrombocytopenic purpura (ITP) was studied. According to the intensity and pattern of cytoplasmic staining, we divided megakaryocytes into at least six groups: (1) low granular (LG), (2) diffuse granular (DG), (3) diffuse dense granular (DDG), (4) marginal granular (MG), (5) denuded (DMK), and (6) endomitotic (EndoM). Most of the megakaryocytes were DG (mean, 42.75% +/- 19.21%) and DDG (mean, 50.25% +/- 21.23%). In correlation with nuclear morphology and cell size, it appears that substances binding to UEA-1 are located in the paranuclear region in early megakaryocytes and produce a low granular focal staining pattern (LG cells). Next, the granules spread throughout the cytoplasm (DG cells) and increase in quantity (DDG). This is followed by migration of granules to the periphery of the cytoplasm (MG cells) and is associated with the liberation of platelets and eventual formation of DMK megakaryocytes. Endomitosis, regulated by unknown factors, occurred in the MG stage. In comparing the group with nonhematologic disease (mean DG, 35.4% +/- 18.48%; DDG, 58.4% +/- 21.8%) and the group with ITP (mean DG, 50.1% +/- 17.82%; DDG, 42.1% +/- 18.12%), we found an increasing proportion of DG megakaryocytes in ITP, which suggests a left-shifted maturation of megakaryocytes. By understanding the staining pattern seen in the different stages of megakaryocytic differentiation, UEA-1 staining may be a practical method for studying megakaryocytopoiesis in routinely processed paraffin sections of bone marrow biopsy samples.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential diagnosis of L26-positive, CD15-negative Hodgkin's disease and large B-cell lymphoma with a high content of reactive T-cells: a morphologic and immunohistochemical study.","authors":"D T Nguyen,&nbsp;L W Diamond,&nbsp;M L Hansmann,&nbsp;R Fischer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>B-cell non-Hodgkin's lymphomas with a marked preponderance of reactive T cells, so-called T-cell rich B-cell lymphomas (TCRBCLs), can be morphologically confused with Hodgkin's disease (HD). To establish helpful distinguishing features in paraffin sections, 10 cases of L26-positive, CD15-negative HD and 10 cases of TCRBCL were compared; 4 cases of HD had morphologic features of the nodular lymphocyte predominant (LP) type. Nine of 10 cases of HD contained fewer than 20 mitoses/20 high power fields (hpf) and only 1 had pericapsular involvement. In contrast, 9 of 10 TCRBCL had greater than 20 mitoses/20 hpf and 7 had perinodal infiltration. HDLP was easily distinguished from TCRBCL by the expanded dendritic meshworks outlining the L & H nodules and the high content of CD57-positive lymphocytes. The remaining 6 cases of non-LP L26-positive HD had a relatively distinctive immunostaining pattern, with absence of CD45 and discordant reactivity for L26 and Ki-B5 in Reed-Sternberg cells and variants. Only 3 cases of TCRBCL had a similar CD45 and L26/Ki-B5 immunostaining pattern, and these could be distinguished by demonstrable cytoplasmic light-chain restriction. These results show that evaluation of the mitotic count, pericapsular involvement, and immunohistochemical staining patterns for Ki-M4p, CD57, L26/Ki-B5, and CD45 can help to discriminate TCRBCL from L26-positive HD when only fixed material is available.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19845412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of interferon treatment on the macrophage population in the bone marrow of patients with Ph1+-CML.","authors":"J Thiele,&nbsp;H M Kvasnicka,&nbsp;T K Zirbes,&nbsp;S E Baldus,&nbsp;O Djuren,&nbsp;H Lienhard,&nbsp;J Lorenzen,&nbsp;L D Leder,&nbsp;N Niederle,&nbsp;R Fischer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In Ph1+-CML the abnormal function of bone marrow stroma was related to the presence of clonally transformed macrophages (MAs). Moreover, previous in vitro studies revealed that activation (phagocytosis, cytotoxicity) of MAs was associated with a pronounced increase in alpha-D-galactosyl residues on their membranes. Stimulation of this cell population has been shown to be easily accomplished by interferon (IFN) treatment. The latter caused an enhanced expression of binding sites for the lectin Griffonia simplicifolia isotype I-B4 (GSA-I), specific for this carbohydrate moiety. The present immuno- and lectinhistochemical study was designed to quantify MA subsets of the bone marrow in patients with Ph1+-CML under IFN therapy. For comparison a control group with monotherapy by busulfan (BU) was included. Identification of the total MA population was carried out by a monoclonal antibody against CD68 (PG-M1) and for the characterization of its activated fraction, the lectin GSA-I was employed. In both therapeutic groups morphometric analysis revealed a conspicuous increase in PG-M1-positive MAs in sequential trephine biopsies. However, following IFN therapy the relative amount of the GSA-I fraction was maintained or even increased and accompanied by enhanced apoptosis. On the other hand, BU generated a significant reduction of this subpopulation and the number of apoptotic cells as well. This finding is probably related to the immunomodulatory activity of IFN associated with MA activation and secretion of biogenic mediators. These are thought to belong partly to the so-called tumor necrosis factor superfamily, which is known to stimulate programmed cell death (apoptosis).</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19999673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy.","authors":"N Straetmans,&nbsp;D D Ma,&nbsp;D F Nevell,&nbsp;C Arthur","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We conducted a retrospective study to assess the changes in bone marrow (BM) stromal antigenic profile and fibrosis in chronic myeloid leukemia (CML) under combined interferon-alpha (IFN) and Ara-c therapy. Bone marrow biopsies were taken before therapy and twice (at 4 and 15 months) during therapy in 10 CML patients and compared with non-CML samples. Collagen and reticulin fibrosis was assessed by histochemical methods and phenotypic changes were studied by immunohistochemistry (APAAP) with antibodies directed against endothelial cell antigens, cell adhesion molecules, and HLA-DR. It was found that: (1) BM endothelial cells in patient and in control specimens showed a specific pattern of antigen expression: high expression of FVIII and CD34 (except on sinusoids for the latter), variable expression of UEA I, and no expression of HLA-DR and E-selectin. (2) Compared to non-CML controls, CML specimens at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopoietic cells. (3) Treatment did not influence BM fibrosis, the vascular content of the BM, or the expression of the antigens tested except an increase in the number of CD34+ sinusoids (5/10 patients), an increase in the number of HLA-DR+, and a decrease in the number of CD34+ hemopoietic cells (6/10). (4) On therapy, difficulty in aspiration and/or reduced BM fragment numbers were noted in 8 of 10 patients whose bone marrow was still normocellular or slightly hypercellular. In conclusion, CML samples at diagnosis showed increased fibrosis and decreased CD31 and CD61 expression compared to controls. During the period of observation, combined therapy did not modify BM fibrosis; however, an increase in CD34+ sinusoids and a decrease in CD34+ hemopoietic cells were noted.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19999674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular diagnosis of hemophilia A in Chinese patients by an analysis of inversions in the factor VIII gene.","authors":"Y D Chen,&nbsp;Y Z Zhang,&nbsp;J S Wu,&nbsp;H L Wang,&nbsp;H Z Shao,&nbsp;Z R Ren,&nbsp;Z Chen,&nbsp;Z Y Wang,&nbsp;Y T Zeng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hemophilia A is an X-linked bleeding disorder caused by deleterious mutations in the factor VIII gene. An inversion caused by introchromosomal homologous recombination between the A gene located in intron 22 of the factor VIII gene and one of the two telomeric A genes has been recently described as the common cause of about 50% of cases of severe hemophilia A. The rearrangement can be readily detected by a Southern blotting procedure. We report use of this procedure to detect rearrangements in 106 unrelated Chinese hemophilia A cases. In 49.3% of the patients with severe disease an inversion was found, but no inversion was detected in any of the patients with moderate or mild disease. The majority of inversions (91.4%) involved the most distal A gene; in a minority (8.6%) the more proximal A gene was involved. These results indicate that intron 22 inversion is the most important molecular defect causing Chinese hemophilia A and that analysis for intron 22 inversion may be the first-line test in the molecular diagnosis of severe hemophilia A.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased expression of the high-affinity receptor for IgG (FcRI, CD64) on neutrophils in multiple myeloma.","authors":"A Ohsaka,&nbsp;K Saionji,&nbsp;S Takagi,&nbsp;J Igari","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The surface expression of effector cell molecules on neutrophils was examined in 19 patients with multiple myeloma (MM), 6 patients with monoclonal gammopathy of undetermined significance (MGUS) and 22 healthy control subjects. The expression of Fc receptors for IgG (FcR), complement receptors (CR), and cellular adhesion molecules on neutrophils was determined by flow cytometry and monoclonal antibodies. MM neutrophils exhibited higher expression of FcRI, CR3, and CR4 and lower expression of FcRII and L-selectin than that in MGUS and controls. Granulocyte colony-stimulating factor (G-CSF, 50 micrograms/m2/d) was administered subcutaneously to 8 patients with MM and to 4 healthy volunteers. G-CSF administration increased the expression of FcRI, FcRII, and CR1 on neutrophils and decreased the expression of FcRIII on neutrophils in both groups. The application of G-CSF also resulted in increase of CR3 and CR4 expression and in decrease of L-selectin expression on neutrophils in healthy volunteers but not in MM patients. These findings suggest that MM neutrophils may be activate in vivo and that effector cell molecular expression on MM neutrophils is further modulated by G-CSF application.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19845413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of flow cytometry in the study of human neutrophil biology and pathology.","authors":"G Carulli","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Flow cytometry represents an interesting methodologic approach to human neutrophil biology and pathology. Several aspects of neutrophil activation can be evaluated by flow cytometry: phagocytosis, respiratory burst (superoxide anion generation, intracellular hydrogen peroxide production), intracellular pH, actin polymerization, membrane potential, aggregation, cytotoxicity, degranulation, and surface marker expression. In several instances whole blood methods have been developed and have been shown to be very specific and sensitive. Neutrophils can easily be distinguished from other circulating cells, including eosinophils, and methods for the evaluation of neutrophil phagocytosis and hydrogen peroxide production are currently used. In addition whole blood procedures for the determination of the expression of neutrophil function-associated surface antigens have been recommended in order to avoid the artifactual changes resulting from isolation methods. Purified neutrophil have to be used to study other parameters such as actin polymerization and cytotoxicity. Flow cytometry permits a multiparametric evaluation of neutrophil functions, and advances in software technology facilitate a wide variety of choices for the handling, storage, and evaluation of data. The applications of flow cytometry in human neutrophil diseases include the diagnosis of chronic granulomatous disease and leukocyte adhesion syndrome types 1 and 2, and the evaluation of granulocyte biology in several clinical conditions such as immunodeficiency conditions, recurrent infections, hematologic diseases, and noninfectious diseases caused by uncontrolled neutrophil activation.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dephosphorylation of a 34kd triton-insoluble F-actin pool protein is associated with phorbol ester-induced actin polymerization in human polymorphonuclear leukocytes.","authors":"R G Watts","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Activation of human polymorphonuclear leukocytes (PMNs) by chemotactic peptide (FMLP) or phorbol ester (PMA) results in actin reorganization and PMN motility. Evidence suggests that PMA and FMLP activate PMN actin reorganization by different mechanisms. For example, the protein phosphatase inhibitor, okadaic acid (OA), inhibits PMA- but not FMLP-induced actin rearrangement, suggesting protein dephosphorylation is key to PMA but not FMLP actin changes and that PMN actin reorganization occurs by multiple mechanisms. Further support for multiple actin polymerization mechanisms is the recent description of distinct F-actin pools coexisting with G-actin in PMNs, Triton insoluble F-actin (TIF) and Triton soluble F-actin (TSF). These studies examine quantitative actin pool-specific actin polymerization in PMA- and FMLP-activated PMNs using quantitative SDS-PAGE and the phosphorylation of proteins in each actin pool using 32P orthophosphate (32P) labeling. The results show: (1) OA alone has no effect on actin pool content; (2) PMA induces actin growth only in the TIF pool similar to results with FMLP, and (3) OA pretreatment has no effect on FMLP actin polymerization, but inhibits PMA-induced changes. 32P results show that in basal PMNs, multiple phosphoproteins are found in the TIF including a protein of MW 34kd (pp34), the TSF pool contains a pp34 and a pp69 and the G-actin pool a pp34. PMA induces dephosphorylation of pp34 in the TIF (0.59 +/- 0.14 x basal, n = 3). OA prior to PMA prevents TIF pp34 dephosphorylation and actin shifts between the TIF, TSF, and G pools. OA alone results in phosphorylation of pp34 in all actin pools but no shift in actin content. The results show that (1) phosphoproteins exist in all three actin pools of PMNs-TIF-actin, TSF-actin, and G-actin; (2) both PMA and FMLP cause quantitatively identical actin polymerization in the TIF; and (3) in contrast, PMA but not FMLP TIF growth requires dephosphorylation of a pp34. This as yet unidentified phosphoprotein appears crucial to PMA- but not FMLP-induced actin polymerization.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response of the blast stem cells of acute myeloblastic leukemia to G-CSF, GM-CSF, or the ligand for C-KIT, alone or in combination.","authors":"E A McCulloch,&nbsp;S Minkin,&nbsp;J E Curtis,&nbsp;M D Minden","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Growth factors are commonly included in protocols for the treatment of acute myeloblastic leukemia (AML). Because the response of blast stem cells in culture to growth factors might influence the contribution of factor to clinical outcome, we studied 42 patients with AML or severe myelodysplasia. Peripheral blood blast cells were cultured in a clonogenic assay at three cell concentrations and with the following combinations of growth factors: no added growth factor (NF), G-CSF, GM-CSF, Kit ligand (KL), G-CSF + KL, GM-CSF + KL, and G-CSF + GM-CSF + KL. The slope of the line relating cell number plated to colony formation was calculated by least squares. The slopes were used to form three equally sized groups of patients. Marked heterogeneity was found in response of the blast populations to factor. A few general conclusions emerged: (1) autonomous blast populations are very rare; (2) although usually a population responds better to one of the growth factors than to others, seldom is the response exclusively to one factor; (3) when more than one factor is included in the cultures, synergism is usually seen. Significant associations were seen between successful remission induction for low slope values in cultures with NF or KL alone. For remission, but not survival, associations were found with intermediate values of slope in cultures with G-CSF + KL and GM-CSF + KL. We conclude that measurements of growth factor response are feasible and yield clinically useful data.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19845410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}