bluuebunny/crossref_metadata_2025_split huggingface dataset:
The α-Chemokine Receptor CXCR4 Is Expressed on the Megakaryocytic Lineage From Progenitor to Platelets and Modulates Migration and Adhesion
Authors: Wang Jian-Feng , Liu Zhong-Ying , Groopman Jerome E. 
Published: October 2019

CXCR4 is the receptor for the α-chemokine stromal cell-derived factor 1 (SDF-1) and has been shown to be expressed on a diversity of leukocytes. In this report, the expression of the CXCR4 receptor in cells of megakaryocytic lineage and the role of SDF-1 in megakaryocytopoiesis were investigated. Using flow cytometry in combination with reverse transcriptase-polymerase chain reaction (RT-PCR), we observed that bone marrow CD34+, CD61+ cells, blood platelets, and megakaryocytic leukemia cell lines all expressed the CXCR4 receptor. To examine the expression of the CXCR4 receptor on megakaryocyte progenitors (colony-forming units-megakaryocyte [CFU-Meg]), CXCR4-positive and -negative CD34+ populations were separated from bone marrow and cultured in a plasma clot culture system. A subpopulation of the CFU-Meg was found in the CXCR4-positive fraction. The functional significance of CXCR4 expression on cells of the megakaryocytic lineage was examined by studying the effects of SDF-1α on migration and proliferation of megakaryocyte progenitor cells in vitro. We found that SDF-1α potently induced megakaryocyte progenitor migration and significantly enhanced adhesion of mature marrow megakaryocytes to endothelium. No marked effects of SDF-1α alone or in combination with thrombopoietin and stem cell factor/kit ligand on megakaryocyte production in vitro were noted. These results demonstrate for the first time that the CXCR4 α-chemokine receptor is expressed on cells of the megakaryocytic lineage from progenitors to platelets and that its ligand SDF-1α may modulate several aspects of megakaryocytopoiesis.© 1998 by The American Society of Hematology.
Expression of Cyclin E and the Cyclin-Dependent Kinase Inhibitor p27 in Malignant Lymphomas—Prognostic Implications
Authors: Erlanson Martin , Portin Cajsa , Linderholm Barbro , Lindh Jack , Roos Göran , Landberg Göran 
Published: October 2019

Cyclin E and the cyclin-dependent kinase inhibitor p27 are two important regulators of the G1-S transition modulating the activity of cyclin-dependent kinases. Aberrations in the cell cycle control are often observed in tumors and might even be mandatory in tumor development. To investigate the importance of cell-cycle defects in malignant lymphomas we have characterized the expression of cyclin E and p27 in 105 newly diagnosed lymphomas using immunohistochemistry. A significant, inverse correlation between p27 and cyclin E expression was observed (rs = −.24, P = .02) and both proteins correlated with the S-phase fraction (rs = −.35, P < .001 andrs = .45, P < .001, respectively). The inverse relationship between p27 expression and proliferation was abrogated in some lymphomas, suggesting that p27 downregulation can represent a genuine aberration. Survival analysis was performed in 105 patients with a median observation time of 86 months. Low p27 and high cyclin E expression were significantly associated with a poor prognosis (P = .0001 and .03, respectively). In a multivariate Cox analysis, p27 expression, stage, serum lactate dehydrogenase level, grade, and age were independent prognostic factors, in contrast to S-phase fraction and cyclin E expression. This is the first report showing that p27 expression in malignant lymphomas has independent prognostic significance, which necessitates future studies regarding its more precise biological role in lymphoid tumorogenesis.
© 1998 by The American Society of Hematology.
Mutual Education Between Hematopoietic Cells and Bone Marrow Stromal Cells Through Direct Cell-to-Cell Contact: Factors That Determine the Growth of Bone Marrow Stroma-Dependent Leukemic (HB-1) Cells
Authors: Jiang Huijie , Sugimoto Kenkichi , Sawada Hitoshi , Takashita Emi , Tohma Maki , Gonda Hiroyuki , Mori Kazuhiro John 
Published: October 2019

A stroma-dependent cell line (HB-1) was established from myelogenous leukemic cells of CBA/N mouse. Characterization of the cells showed that HB-1 proliferated on hematopoietic supportive stromal cells (MS-10), but did not survive or proliferate on hematopoietic nonsupportive cells (MS-K). Direct contact between HB-1 and MS-10 appears to be necessary for HB-1 to proliferate on MS-10. We found that interleukin-1α (IL-1α) produced by MS-10 plays a major role in the survival and proliferation of HB-1. IL-11 did not support the proliferation of HB-1 cells by itself, but enhanced the proliferation of HB-1 cells in the presence of IL-1α. The expression of IL-1α and IL-11 was induced in MS-10 by the direct contact with HB-1 cells, and the expression of IL-1 receptor type I (IL-1RI) and interleukin-11 receptor (IL-11R) was induced in HB-1 cells by the attachment of the cells to MS-10. These findings show the existence of two-way interactions between HB-1 and MS-10.© 1998 by The American Society of Hematology.
CD164, a Novel Sialomucin on CD34+ and Erythroid Subsets, Is Located on Human Chromosome 6q21
Authors: Watt Suzanne M. , Bühring Hans-Jörg , Rappold Irene , Chan James Yi-Hsin , Lee-Prudhoe Jane , Jones Tania , Zannettino Andrew C.W. , Simmons Paul J. , Doyonnas Regis , Sheer Denise , Butler Lisa H. 
Published: October 2019

CD164 is a novel 80- to 90-kD mucin-like molecule expressed by human CD34+ hematopoietic progenitor cells. Our previous results suggest that this receptor may play a key role in hematopoiesis by facilitating the adhesion of CD34+ cells to bone marrow stroma and by negatively regulating CD34+hematopoietic progenitor cell growth. These functional effects are mediated by at least two spatially distinct epitopes, defined by the monoclonal antibodies (MoAbs), 103B2/9E10 and 105A5. In this report, we show that these MoAbs, together with two other CD164 MoAbs, N6B6 and 67D2, show distinct patterns of reactivity when analyzed on hematopoietic cells from normal human bone marrow, umbilical cord blood, and peripheral blood. Flow cytometric analyses revealed that, on average, 63% to 82% of human bone marrow and 55% to 93% of cord blood CD34+ cells are CD164+, with expression of the 105A5 epitope being more variable than that of the other identified epitopes. Extensive multiparameter flow cytometric analyses were performed on cells expressing the 103B2/9E10 functional epitope. These analyses showed that the majority (>90%) of CD34+ human bone marrow and cord blood cells that were CD38lo/− or that coexpressed AC133, CD90(Thy-1), CD117(c-kit), or CD135(FLT-3) were CD164(103B2/9E10)+. This CD164 epitope was generally detected on a significant proportion of CD34+CD71lo/− or CD34+CD33lo/− cells. In accord with our previous in vitro progenitor assay data, these phenotypes suggest that the CD164(103B2/9E10) epitope is expressed by a very primitive hematopoietic progenitor cell subset. It is of particular interest to note that the CD34+CD164(103B2/9E10)lo/−cells in bone marrow are mainly CD19+ B-cell precursors, with the CD164(103B2/9E10) epitope subsequently appearing on CD34lo/−CD19+ and CD34lo/−CD20+ B cells in bone marrow, but being virtually absent from B cells in the peripheral blood. Further analyses of the CD34lo/−CD164(103B2/9E10)+ subsets indicated that one of the most prominent populations consists of maturing erythroid cells. The expression of the CD164(103B2/9E10) epitope precedes the appearance of the glycophorin C, glycophorin A, and band III erythroid lineage markers but is lost on terminal differentiation of the erythroid cells. Expression of this CD164(103B2/9E10) epitope is also found on developing myelomonocytic cells in bone marrow, being downregulated on mature neutrophils but maintained on monocytes in the peripheral blood. We have extended these studies further by identifying Pl artificial chromosome (PAC) clones containing the CD164 gene and have used these to localize the CD164 gene specifically to human chromosome 6q21.© 1998 by The American Society of Hematology.
Negative Regulation by Interleukin-3 (IL-3) of Mouse Early B-Cell Progenitors and Stem Cells in Culture: Transduction of the Negative Signals by βc and βIL-3 Proteins of IL-3 Receptor and Absence of Negative Regulation by Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Matsunaga Takuya , Hirayama Fumiya , Yonemura Yuji , Murray Richard , Ogawa Makio 
Published: October 2019

The receptors for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 share a common signaling subunit βc. However, in the mouse, there is an additional IL-3 signaling protein, βIL-3, which is specific for IL-3. We have previously reported that IL-3 abrogates the lymphoid potentials of murine lymphohematopoietic progenitors and the reconstituting ability of hematopoietic stem cells. We used bone marrow cells from βc- and βIL-3–knock-out mice to examine the relative contributions of the receptor proteins to the negative regulation by IL-3. First, we tested the effects of IL-3 on lymphohematopoietic progenitors by using lineage-negative (Lin−) marrow cells of 5-fluorouracil (5-FU)-treated mice in the two-step methylcellulose culture we reported previously. Addition of IL-3 to the combination of steel factor (SF, c-kit ligand) and IL-11 abrogated the B-lymphoid potential of the marrow cells of both types of knock-out mice as well as wild-type mice. Next, we investigated the effects of IL-3 on in vitro expansion of the hematopoietic stem cells. We cultured Lin−Sca-1–positive, c-kit–positive marrow cells from 5-FU–treated mice in suspension in the presence of SF and IL-11 with or without IL-3 for 7 days and tested the reconstituting ability of the cultured cells by transplanting the cells into lethally irradiated Ly-5 congenic mice together with “compromised” marrow cells. Presence of IL-3 in culture abrogated the reconstituting ability of the cells from both types of knock-out mice and the wild-type mice. In contrast, addition of GM-CSF to the suspension culture abrogated neither B-cell potential nor reconstituting abilities of the cultured cells of wild-type mice. These observations may have implications in the choice of cytokines for use in in vitro expansion of human hematopoietic stem cells and progenitors.© 1998 by The American Society of Hematology.
Clonal Diversity of Ig and T-Cell–Receptor Gene Rearrangements Identifies a Subset of Childhood B-Precursor Acute Lymphoblastic Leukemia With Increased Risk of Relapse
Authors: Green Elaine , McConville Carmel M. , Powell Judith E. , Mann Jillian R. , Darbyshire Philip J. , Taylor A. Malcolm R. , Stankovic Tatjana 
Published: October 2019

Current prognostic indicators such as age, sex, and white blood cell count (WBC) fail to identify all children with more aggressive forms of B-precursor acute lymphoblastic leukemia (ALL), and a proportion of patients without poor prognostic indicators still relapse. Results obtained from an analysis of 65 pediatic B-precursor ALL patients indicated that subclone formation leading to clonal diversity, as detected by Ig and T-cell receptor (TCR) gene rearrangements, may represent a very useful prognostic indicator, independent of age, sex, and WBC. Disease-free survival was significantly shorter in those patients showing clonal diversity at presentation. Furthermore, clonal diversity was detected not only in the majority of high-risk patients who relapsed but was also associated with a high probability of relapse in standard-risk patients. Sixty-five percent (13/20) of standard-risk patients who also showed clonal diversity subsequently relapsed, whereas the percentage of relapses among standard-risk patients without clonal diversity was much lower at 19% (7/36). Continued clonal evolution during disease progression is an important feature of aggressive B-precursor ALL. All 5 patients with clonal diversity who were followed up in our study showed a change in the pattern of clonality between presentation and relapse. This implies an important role for clonal diversity as a mechanism of disease progression through the process of clonal variation and clonal selection.
© 1998 by The American Society of Hematology.
MDM2 Protein Overexpression Inhibits Apoptosis of TF-1 Granulocyte-Macrophage Colony-Stimulating Factor–Dependent Acute Myeloblastic Leukemia Cells
Authors: Urashima Mitsuyoshi , Teoh Gerrard , Chauhan Dharminder , Ogata Atsushi , Shirahama Shuya , Kaihara Chiharu , Matsuzaki Masaharu , Matsushima Hiroshi , Akiyama Masaharu , Yuza Youki , Maekawa Kihei , Anderson Kenneth C. 
Published: October 2019

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for acute myeloblastic leukemia (AML) cells. Murine double minute 2 (MDM2) oncoprotein, a potent inhibitor of wild-type p53 (wtp53), can function both to induce cell proliferation and enhance cell survival, and is frequently overexpressed in leukemias. Therefore, we focused on the importance of MDM2 protein in GM-CSF–dependent versus GM-CSF– independent growth of AML cells. The TF-1 AML cell line, which has both wtp53 and mutant p53 genes, showed GM-CSF–dependent growth; deprivation of GM-CSF resulted in G1 growth arrest and apoptosis. MDM2 mRNA and protein were highly expressed in proliferating TF-1 cells in the presence of GM-CSF and decreased significantly with deprivation of GM-CSF. In contrast, p53 protein increased with GM-CSF deprivation. Ectopic overexpression of MDM2 in TF-1 AML cells conferred resistance to GM-CSF deprivation, and is associated with decreased p53 protein expression. Moreover, a variant of TF-1 cells that grows in a GM-CSF–independent fashion also expressed high levels of MDM2 and low levels of p53. These results suggest that GM-CSF–independent growth of AML cells is associated with overexpression of MDM2 protein and related modulation of p53 expression.© 1998 by The American Society of Hematology.
A Single Genetic Origin for the Common Prothrombotic G20210A Polymorphism in the Prothrombin Gene
Authors: Zivelin Ariella , Rosenberg Nurit , Faier Shlomit , Kornbrot Nurit , Peretz Hava , Mannhalter Christine , Horellou Marie Helene , Seligsohn Uri 
Published: October 2019

The polymorphism G20210A in the 3′ untranslated region of the prothrombin gene is associated with an increased level of factor II activity and confers a twofold to fivefold increase in the risk for venous thromboembolism. Among Caucasian populations, the prevalence of factor II G20210A heterozygotes is 1% to 6%, whereas in non-Caucasian populations it is very rare or absent. The aim of the present study was to discern whether factor II G20210A originated from a single or recurrent mutational events. Allele frequencies of four dimorphisms spanning 16 of 21 kb of the factor II gene were determined in 133 unrelated Caucasian subjects of Jewish, Austrian, and French origins who bore factor II G20210A (10 homozygotes and 123 heterozygotes) and 110 Caucasian controls. Remarkable differences in the allele frequencies for each dimorphism were observed between the study groups (P = .0007 or less), indicating strong linkage disequilibrium and suggesting a founder effect. Indeed, a founder haplotype was present in 68% of 20210A mutant alleles and only in 34% of 20210G normal alleles (P < .0001). These data strongly support a single origin for factor II G20210A that probably occurred after the divergence of Africans from non-Africans and of Caucasoid from Mongoloid subpopulations.© 1998 by The American Society of Hematology.
ABI-1, a Human Homolog to Mouse Abl-Interactor 1, Fuses theMLL Gene in Acute Myeloid Leukemia With t(10;11)(p11.2;q23)
Authors: Taki Tomohiko , Shibuya Noriko , Taniwaki Masafumi , Hanada Ryoji , Morishita Kazuhiro , Bessho Fumio , Yanagisawa Masayoshi , Hayashi Yasuhide 
Published: October 2019

Recurrent translocation t(10;11) has been reported to be associated with acute myeloid leukemia (AML). Recently, two types of chimeric transcripts, MLL-AF10 in t(10;11)(p12;q23) andCALM-AF10 in t(10;11)(p13;q14), were isolated. t(10;11) is strongly associated with complex translocations, including invins(10;11) and inv(11)t(10;11), because the direction of transcription of AF10 is telomere to centromere. We analyzed a patient of AML with t(10;11)(p11.2;q23) and identified ABI-1 on chromosome 10p11.2, a human homolog to mouse Abl-interactor 1 (Abi-1), fused with MLL. Whereas the ABI-1 gene bears no homology with the partner genes of MLL previously described, the ABI-1 protein exhibits sequence similarity to protein of homeotic genes, contains several polyproline stretches, and includes asrc homology 3 (SH3) domain at the C-terminus that is required for binding to Abl proteins in mouse Abi-1 protein. Recently, e3B1, an eps8 SH3 binding protein 1, was also isolated as a human homolog to mouse Abi-1. Three types of transcripts of ABI-1 gene were expressed in normal peripheral blood. Although e3B1 was considered to be a full-length ABI-1, the MLL-ABI-1fusion transcript in this patient was formed by an alternatively spliced ABI-1. Others have shown that mouse Abi-1 suppresses v-ABL transforming activity and that e3B1, full-length ABI-1, regulates cell growth. In-frame MLL-ABI-1 fusion transcripts combine the MLL AT-hook motifs and DNA methyltransferase homology region with the homeodomain homologous region, polyproline stretches, and SH3 domain of alternatively spliced transcript of ABI-1. Our results suggest that the ABI-1 gene plays a role in leukemogenesis by translocating to MLL.
© 1998 by The American Society of Hematology.
Transformation of Mycosis Fungoides/Sezary Syndrome: Clinical Characteristics and Prognosis
Authors: Diamandidou Eleni , Colome-Grimmer Maria , Fayad Luis , Duvic Madeleine , Kurzrock Razelle 
Published: October 2019

The occurrence of large cell transformation has been well documented in a subgroup of patients with mycosis fungoides/Sezary syndrome (MF/SS). However, because of the rarity of MF/SS, little is known about the influence of clinicopathologic features in predicting large cell transformation and about outcome in the transformed cases. We evaluated all patients with MF/SS who were registered in our clinic during the study period and for whom pathologic slides for review were available or could be obtained. Disease was classified as transformed if biopsy showed large cells (≥4 times the size of a small lymphocyte) in more than 25% of the infiltrate or if they formed microscopic nodules. Twenty-six patients with transformation were identified from a total of 115 evaluable cases with a diagnosis of MF/SS. The actuarial cumulative probability of transformation reached 39% in 12 years. The median time from diagnosis of MF/SS to transformation was 12 months (range, 0 to 128 months). Thirty-one percent of all patients with stage IIB-IV disease at presentation eventually transformed versus 14% of those with stage I-IIA (P= .03), with transformation being especially common in patients with tumors (T3), 46% of whom transformed. Combining elevated β2 microglobulin and lactic dehydrogenase (neither elevated v one or both elevated) was also predictive for transformation (P = .009). The median survival from initial diagnosis of MF/SS for the transformed patients was 37 months versus 163 months for the untransformed group (P = .0029). The median survival from transformation was 19.4 months (range, 2+ to 138 months). The following characteristics were associated with an inferior survival in transformed patients: (1) early transformation (<2 years from the diagnosis v ≥2 years; P = .011) and (2) advanced stage (IIB-IV v I-IIA; 2-year survival, 23% v 86%;P = .0035). We conclude that MF/SS patients with stages IIB-IV disease and, in particular, those with tumors have a high incidence of large-cell transformation. Patients with transformation have a relatively poor survival, especially if transformation occurs early (within 2 years) in the course of disease or if they are staged as IIB or higher.
© 1998 by The American Society of Hematology.
Second Malignancies in Patients With Hairy Cell Leukemia in British Columbia: A 20-Year Experience
Authors: Au Wing Y. , Klasa Richard J. , Gallagher Richard , Le Nhu , Gascoyne Randy D. , Connors Joseph M. 
Published: October 2019

The purpose of this study was to compare the relative risk of second malignancies in a cohort of patients with hairy cell leukemia (HCL) against the normal population. Potential effects of type of treatment and duration of follow-up and the site distribution of cancer were also examined. Between 1976 and 1996, 117 patients were diagnosed with HCL in British Columbia who were referred to the British Columbia Cancer Agency (BCCA) for treatment. All additional malignancies were traced using a provincial population-based cancer registry and follow-up records from the BCCA. There were 90 men and 27 women. Median age at diagnosis was 53 years. The median follow-up time was 68 months. Twenty-three patients underwent primary splenectomy, 65 received interferon alpha, 24 deoxycoformycin, and 67 cladribine (2-chlorodeoxyadenosine). Thirty-six patients had an additional malignancy (30.7%) with a total of 44 tumors. Six patients (5.1%) had two or more malignancies. Twenty-five patients had malignancies diagnosed after HCL (21.3%), three concurrent with HCL (2.6%), and 12 preceding HCL (10.2%). Second tumors (n = 28 tumors) occurred at a median of 40 months after HCL (range, 3 to 167). The relative rate (RR) of second malignancy among men and women was 2.91 (P < .001) and 1.65 (P = .23), respectively, compared with age and secular trend-matched controls. There were eight prostate cancers, nine nonmelanoma skin cancers, two lung cancers, and four gastrointestinal adenocarcinomas. The RR (90% confidence interval [CI]) in the various treatment groups were: splenectomy (RR = 0.21 to 3.81), purine analogues (RR = 0.60 to 5.69), interferon then purine analogues (RR = 1.60 to 4.31), interferon alone (RR = 1.57 to 8.40). Cancer risk peaked at 2 years after HCL (RR = 4.13) and fell steadily afterwards, reaching a RR of 1.82 at 6 years. Twenty patients died, six due to HCL, 10 due to second malignancies, and four of unrelated causes. HCL patients appear to be inherently prone to malignancies. This appears to be more related to HCL tumor burden than to genetic predisposition or treatment effect. RR tends to fall with time after effective treatment. However, close monitoring for and vigorous prevention of cancer in HCL patients is advisable.
© 1998 by The American Society of Hematology.