摘要:

AbstractThere exists a wide variety of lymphoid leukemias derived from B and T lymphocytes. These diseases have distinct immunologic and biologic features as well as varied responses to therapeutics. The most common lymphoid leukemia is chronic lymphocytic leukemia (CLL) which is a clonal proliferation of a subset of B cells expressing the CD5 antigen. Prolymphocytic leukemia is usually derived from B cells and shares some features with CLL but is clearly a distinct entity. Hairy‐cell leukemia is a B cell malignancy that is uniquely responsive to a variety of biologic and chemotherapeutic agents. Waldenström's macroglobulinemia is a B cell malignancy that secretes immunoglobulin M (IgM) and may present with the hyperviscosity syndrome. Other B cell malignancies that less commonly present as leukemias include non‐Hodgkin's lymphomas such as follicular lymphoma or mantle zone lymphoma. Multiple myeloma may rarely present or evolve into a plasma cell leukemia, typically in far advanced disease. T cell malignancies that may present as chronic lymphoid leukemias, and in the past have often been referred to as T cell chronic lymphocytic leukemia, are large granular lymphocytic leukemia, adult T cell leukemia/lymphoma, Sézary cell leukemia and rare cases of non‐Hodgkin's lymphoma that are T cell derived and may present or evolve into a leukemic phase. There is also a rare T cell counterpart of prolymphocytic leukemia. Distinguishing these diseases is critical for optimal care of these p

ISSN:1066-5099    

DOI:10.1002/stem.5530130103

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAcute promyelocytic leukemia (APL) is a good model for studying the human malignancies in that up to 90% of APL patients can achieve complete remission (CR) with a differentiation inducer, all‐trans retinoic acid (ATRA). APL is also associated with a specific chromosomal translocation t(15;17) which fuses the retinoic acid receptor α (RARα) gene with a chromosome 15q locus, PML. Recently the RARα and the PML gene structural alterations in t(15;17) have been characterized. The heterogeneity of the PML rearrangements juxtaposes different PML gene portions to the same set of RARα exons, producing two major PML‐RARα fusion mRNA isoforms. A retrotranscriptase/polymerase chain reaction (RT‐PCR) analysis of the fusion transcripts has been developed which allows the detection of minimal residual disease during the clinical remission of APL. Molecular study showed PML‐RARα can form heterodimers with wild‐type PML and RXR. Recently, PML has been shown to be one of the components of a nuclear body, POD. In APL, the normal organization of POD is disrupted by PML‐RARα, whereas ATRA treatment in vivo and in vitro can induce a reorganization of this organelle. Cytogenetic and molecular study allowed a variant translocation t(11;17) being recently discovered in a small subset of APL. This time RARα is fused to a new gene, PLZF, on chromosome 11q23. It has been shown that the PLZF‐RARα, like PML‐RARα, has a “dominant negative” effect on the wild‐type RAR‐RXR. Clinical data obtained from a group of t(11;17) APL patients showed that these respond poorly to ATRA and could be grouped in a special clinical syndrome within APL. The comparison of the biological activities mediated by PML‐RARα and PLZF‐RARα may give new insights into the pathogenesis as well as the mechanisms

ISSN:1066-5099    

DOI:10.1002/stem.5530130104

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe anemia found in patients with chronic infectious, inflammatory and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines which mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin 1 and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin and abnormal mobilization of reticuloendothelial iron stores. Improved understanding of the role played by cytokines in the pathogenesis of ACD may lead to the development of more specific therapy for this syndrome.

ISSN:1066-5099    

DOI:10.1002/stem.5530130105

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractDynamic regulation of receptor function is a distinguishing feature of the integrin family of adhesion molecules and makes a significant contribution to alterations in cellular adhesive properties. The best characterized example is that of the platelet receptor αIIbβ3 (glycoprotein IIb‐IIIa), which does not bind soluble fibrinogen on resting platelets. Following platelet activation, the αIIbβ3 binds soluble fibrinogen with moderately high affinity and platelet aggregation ensues. Similar regulation of receptor function has also been directly demonstrated for α5β1 and αMβ2, and it is likely that it is a general property of all members of the family. The altered ligand binding affinity is due to a change in the conformation of the external domain of the receptor, in response to intracellular signals that are transmitted the length of the molecule. The cytoplasmic tails of the integrins are active participants in this regulation, and they also mediate interactions with the cytoskeleton. A number of anti‐integrin monoclonal antibodies have been described which induce high affinity ligand binding, and certain of these preferentially bind to the high affinity conformation of the receptor. The alteration in conformation allows better access for macromolecular ligands to the ligand binding pocket, which has been mapped (in αIIbβ3) to the amino terminal globular head of the receptor. The precise mechanism by which the activating signal is transferred from within the cell to the distal external domain remains the subject of ac

ISSN:1066-5099    

DOI:10.1002/stem.5530130106

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractInterleukin 12 (IL‐12), or natural killer cell stimulatory factor (NKSF), has multiple biologic effects on T lymphocytes and natural killer cells. In this study, we evaluated the effect of IL‐12 on human hematopoiesis by analyzing the growth of CD34+33‐cells in methylcellulose culture with or without serum. Blood cells were collected by apheresis from an expanded stem cell pool during the rebound phase of hematopoiesis after chemotherapy and purified by combined purification procedures to yield target CD34+33‐cells. IL‐12, by itself or in combination with IL‐3 and erythropoietin (Epo), had no effect on the formation of colonies from the unfractionated blood mononuclear cells. In the presence of fetal bovine serum (FBS), IL‐12 increased the number of colony forming units for granulocyte‐macrophage (CFU‐GM) from CD34+33‐cells which responded to IL‐3, but not the number of CFU‐GM from those which responded to stem cell factor (SCF) or granulocyte colony stimulating factor (G‐CSF). This effect was not abolished by the addition of monoclonal antibodies against tumor necrosis factor α (TNF‐α), interferon‐γ (IFN‐γ), IL‐1α, IL‐6, G‐CSF, or granulocyte/macrophage CSF (GM‐CSF). However, the stimulatory effect of IL‐12 was abolished in secondary plating in serum‐containing methylcellulose culture after short‐term (48 h) liquid incubation with IL‐3. On the other hand, in serum‐depleted culture containing IL‐3, IL‐12 showed no stimulatory effect on colony growth with or without other cytokines, including SCF, IL‐1α, IL‐6, G‐CSF, GM‐CSF and IFN‐γ. These results suggest that, in the presence of unidentified cytokine(s) in serum, IL‐12 potentiates the stimulatory effect of IL‐3 on human hematopoies

ISSN:1066-5099    

DOI:10.1002/stem.5530130107

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn August, 1992, we established a leukemic cell line (NS‐Meg) from a patient in megakaryoblastic transformation of Philadelphia chromosome‐positive chronic myeloid leukemia. The NS‐Meg cells were positive for α‐naphthyl acetate esterase and periodic acid‐Schiff (PAS) staining and for surface CD4, CD7, CD13, CD34, CD41a, and glycophorin A antigens. Ultrastructurally, the cells had α‐granules, demarcation membranes, and platelet peroxidase activity. The NS‐Meg cells spontaneously produced platelet‐like particles which contained α‐granules, mitochondria and dense bodles, strongly suggesting platelet production. Erythropoietin (Epo), granulocyte/macrophage colony stimulating factor(GM‐CSF), and interleukin 3 (IL‐3) promoted the growth of NS‐Meg cells. Phorbol‐12‐myristate‐13‐acetate increased the expression of both CD41a and CD61 antigens. Ten‐day exposure to Epo induced mature erythroblasts and red cells. These benzidine‐positive cells were positive for hemoglobin F staining. Untreated NS‐Meg cells expressed mRNA for the Epo receptor (EpoR), for GATA‐1, and for α1, α2and γ globin genes. These results indicate that NS‐Meg cells undergo terminal differentiation of both megakaryocyte and erythroid lineages. This cell line should be a very useful tool for the investigation

ISSN:1066-5099    

DOI:10.1002/stem.5530130108

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of this study was to determine how stem cell factor (SCF) modifies hemopoietic cell production. First we determined the effects of a prolonged SCF administration on murine hemopoiesis and analyzed the results by a mathematical simulation model of hemopoiesis in order to explain the data. Subsequently we investigated the effects of simultaneous coadministration of SCF + erythropoietin (Epo), to see how effects of early and late cytokines superimpose. SCF administration during 14 days induced a proliferative wave through the hemopoietic system; colony forming units‐granulocytge macrophage (CFU‐GM), burst forming units‐erythroid (BFU‐E) and colony forming units erythroid (CFU‐E) were the first to be augmented, followed by their respective progeny, ultimately leading to increased blood cell numbers. Despite continued treatment most cell numbers returned to normal values in 14 days, colony forming units‐spleen (CFU‐S), however, remained elevated. This wave pattern could be explained within the framework of a previously established mathematical model of hemopoiesis, if it was assumed that SCF affected the cycling status of primitive cells and if regulatory feedback loops of erythroid and myeloid progenitors on these cells were also allowed.Simultaneous SCF and Epo administration led to synergistic effects on CFU‐E numbers and hematocrit values at moderate Epo doses. At high Epo doses, however, this was less pronounced. We conclude that SCF increases the input into committed hemopoietic lineages, where late acting cytokines can induce furthe

ISSN:1066-5099    

DOI:10.1002/stem.5530130109

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractWe investigated the possible relationship between immunohistochemically detected p53 expression and in vitro response to γ‐irradiation in 24 primary cultures of human ovarian cancers and cutaneous melanomas. The frequency of p53‐positive tumors was around 60% within each tumor histotype. The range of the surviving fraction at 2 Gy (SF2) was similar in p53‐positive (0.10‐0.76) and p53‐negative (0.23‐0.65) tumors, with median values of 0.36 and 0.33, respectively. No differences were observed in the accumulation of DNA‐double strand breaks, assessed by neutral filter elution after exposure to 50 Gy, between p53‐positive and p53‐negative tumors. As regards DNA lesion repair, after 2 h of recovery the percentage of rejoined DNA‐double strand breaks ranged from 19% to 99% in the different cultures, but again the distribution of values was similar for p53‐positive and p53‐negative tumors. Specifically, the median percentage of repaired DNA‐double strand breaks was 70% and 74% in the two groups. On the whole, our data do not support the hypothesis that p53 overexpression is a major determinant of i

ISSN:1066-5099    

DOI:10.1002/stem.5530130110

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530130112

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530130113

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY