bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biphenotypic leukemic lymphocyte precursors in CD2+CD19+ acute lymphoblastic leukemia and their putative normal counterparts in human fetal hematopoietic tissues
Authors: Uckun FM , Muraguchi A , Ledbetter JA , Kishimoto T , O'Brien RT , Roloff JS , Gajl- Peczalska K , Provisor A , Koller B 
Published: October 2019

Abstract
During detailed immunophenotypic analyses of marrow blasts from 336 acute lymphoblastic leukemia (ALL) patients, a very small percentage of cases reactive with B-cell-directed as well as T-cell-directed monoclonal antibodies (MoAbs) were identified. Five ALL cases were biphenotypic since they coexpressed CD2 (Tp50) and CD19 (Bp95) antigens at the single-cell level. The composite immunophenotype of these biphenotypic ALL cases was [TdT+HLA-ABC+CD2+CD3-CD10+CD13-CD14-CD16- CD19+CD20+ ++-CD21-CD33-CD34+Bgp95-C mu- slg-]. Low-molecular-weight B- cell growth factor (LMW-BCGF), recombinant interleukin-2 (rIL-2), and rIL-3 stimulated the proliferative activity of biphenotypic leukemic lymphocyte precursors without inducing differentiation. In the presence of the phorbol ester TPA, leukemic blasts from two cases differentiated along the B precursor pathway to the [CD2-CD10+CD19+CD20+C mu+slg-] pre- B cell stage. Biphenotypic ALL cases did not share a common configuration and gene rearrangement pattern of the immunoglobulin heavy chain genes or T-cell receptor (TCR) genes. Three cases had rearranged C mu genes but germline TCR genes, one case showed rearrangement of both C mu and TCR genes, and the remaining case had rearranged TCR genes but germline C mu genes. All five patients attained prompt remission after standard induction chemotherapy. Three to four years after initial diagnosis, four patients are now off chemotherapy and remain alive in their first remission. One patient relapsed at 3 years, 7 months, but promptly achieved complete remission after reinduction chemotherapy and remains in second remission off chemotherapy greater than 3 years after her reinduction therapy. With two-color immunofluorescence staining techniques and multiparameter flow cytometric analyses, we identified a small population of CD2+CD19+ lymphoid cells in fetal livers (FLs) and fetal bone marrows (FBMs), which may represent the putative normal counterparts of biphenotypic ALL blasts. A CD2+CD19+ normal biphenotypic lymphoid precursor cell line, designated FL 8.2 CD2+, was established from an FL of 8-weeks of gestational age by Epstein-Barr virus (EBV)-induced blastoid transformation. The composite immunophenotype of FL 8.2 CD2+ cell line was [TdT+HLA-ABC+HLA-DR+ CD2+CD5-CD7-CD10+/-CD13-CD19+CD20-CD21+ CD22+CD33-CD34+/-Bgp95-CDw40+C mu-slgD-slgM-]. FL 8.2 CD2+ cells showed germline patterns of immunoglobulin heavy-chain joining region, heavy- chain constant region, kappa light-chain constant region genes, and TCR beta-chain genes. Cross-linking of CD2 as well as CD19 antigens on FL 8.2 CD2+ cells caused an increase of intracellular ionized calcium.(ABSTRACT TRUNCATED AT 400 WORDS)
Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging
Authors: Gulliya KS , Pervaiz S 
Published: October 2019

Abstract
Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin’s lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray- irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested. These results may have therapeutic relevance in patients undergoing interferon treatment who require bone marrow transplantation, as the complete elimination of tumor cells by marrow-purging procedures may be hampered by this increased survival in the presence of interferon.
Plasma cell myeloma--new biological insights and advances in therapy
Authors: Barlogie B , Epstein J , Selvanayagam P , Alexanian R 
Published: October 2019

Abstract
Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with “LDH phenotype,” which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M levels) and biology. Further studies of cellular and molecular biology (ie, CAL- LA, H-ras) may reveal those tumor cell features that define clinical entities, response to therapy, and long-term prognosis. The lack of a major advance in prognosis despite the use of more drugs and more intensive regimens justifies the continued use of standard melphalan- prednisone for patients with a highly favorable prognosis, for the very aged, and for those with a short life expectancy due to other major medical problems. However, a radical departure from standard practice is required to improve the prognosis for younger patients with poor risk features.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of lymphocyte homing receptor as a mechanism of dissemination in non-Hodgkin's lymphoma
Authors: Pals ST , Horst E , Ossekoppele GJ , Figdor CG , Scheper RJ , Meijer CJ 
Published: October 2019

Abstract
To investigate whether the lymphocyte homing receptor (LHR), an adhesion molecule believed to play an important role in the control of normal lymphocyte circulation, influences the spread of non-Hodgkin's lymphoma (NHL), expression of LHR was examined in 107 NHL of various histologic and immunophenotypic subclasses. This analysis revealed that whereas NHL with a putative derivation from recirculating mature T and B lymphocytes almost invariably express high levels of LHR, those akin to sessile mature or immature lymphocytes tend to express lower levels of LHR. Furthermore, in a survey among diffuse large-cell lymphomas of the B-lineage, the tumors of 11 of 13 patients with stage III/IV disease expressed moderate to high levels of LHR, whereas only two of 17 patients with stage I/II disease had tumors that did so. These findings suggest that LHR is involved in the dissemination of NHL.
Differential expression of MHC class II antigens in myelomonocytic leukemia cell lines
Authors: Yunis JJ , Band H , Bonneville F , Yunis EJ 
Published: October 2019

Abstract
Major histocompatibility complex (MHC) class II antigens are discordantly expressed on hematopoietic progenitor cells. Their expression is linked to differential responsiveness of the cells to growth factors and inhibitors. We examined the expression of different MHC class II antigens in a panel of human myelomonocytic cell lines representing different stages of differentiation, by cytofluorographic analysis with monoclonal antibody (MoAb) and Northern blot analysis with specific cDNA probes. These analyses revealed discordant expression of different MHC class II antigens both in basal state and after gamma-IFN induction. Thus KG-1 myeloblast cells express all class II antigens (DR greater than DP greater than DQ) constitutively and their expression increased after gamma-IFN treatment. KG-1a, an immature blast variant of KG-1, does not express class II antigens, even after gamma-IFN treatment. THP-1, a monocytic cell line expresses DR but not DP or DQ under basal conditions. DP and DQ are, however, gamma-IFN inducible. The class II negative HL-60 promyelocytic cell line, expresses DR and DP but not DQ after gamma-IFN induction. In all the above cell lines, surface expression of class II antigens correlated with the levels of mRNA expression as determined with specific cDNA probes. In U-937, a monocytic cell line, no surface expression of class II MHC antigens was observed either with or without gamma-IFN, however, specific mRNA message was observed under basal conditions and was further increased with gamma-IFN, indicating a possible defect in assembly or transport of class II antigens. The patterns of class II MHC antigens in these leukemic cell lines may be a useful model to delineate molecular basis of discordant MHC class II expression during myelomonocytic differentiation.
Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II
Authors: Gramzinski RA , Broze GJ Jr , Carson SD 
Published: October 2019

Abstract
Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate (“thromboplastin”) or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.
Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital
Authors: Cunningham I , Gee TS , Reich LM , Kempin SJ , Naval AN , Clarkson BD 
Published: October 2019

Abstract
Fifty-seven adult patients with acute promyelocytic leukemia (APL) were treated between 1974 and 1984 with daunorubicin (DNR) or 4-(9- acridinylamino)methanesulfan-m-anisidide (AMSA) in combination with arabinosylcytosine (Ara-C) and 6-thioguanine (TG); they also received prophylactic heparin. Forty-one patients (72%) achieved complete remission (CR), including 11 of 12 patients who received the AMSA- containing regimen. The incidence of early fatal hemorrhage was 14%, lower than that of earlier studies or other published reports. Elevated WBC and serum lactate dehydrogenase levels at diagnosis were associated with an increased incidence of life-threatening hemorrhage and shorter remission duration. Advanced age was an unfavorable prognostic factor for male patients. Both DNR and AMSA in combination protocols are effective treatments for APL. The incidence of CR is similar to that achieved in other types of acute nonlymphoblastic leukemia (ANLL) with the same protocols, but the median duration of remission is significantly longer in APL (24 v 9 months) and the percentage of remissions longer than 60 months is also higher in APL (35% v 5%).
Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia
Authors: Digel W , Stefanic M , Schoniger W , Buck C , Raghavachar A , Frickhofen N , Heimpel H , Porzsolt F 
Published: October 2019

Abstract
The biologic effects of recombinant tumor necrosis factor-alpha (rTNF- alpha) and the expression of specific TNF membrane receptors on isolated neoplastic B cells from previously untreated patients with chronic lymphocytic leukemia (CLL) were investigated in vitro. Isolated B cells were incubated up to six days with various concentrations of rTNF-alpha (0.1 to 100 ng/mL). B cells from most patients proliferated ranged from two to 104 times that of unstimulated cells from the same patients. An optimal proliferative effect was achieved at 25 ng/mL rTNF- alpha and an incubation time between 96 and 120 hours, whereas a low concentration of rTNF-alpha (1 ng/mL) reduced [3H]TdR incorporation in four cases. Metaphase cells were detected in the rTNF-alpha-stimulated cultures that proliferated in response to rTNF-alpha. B cells from three of ten patients proliferated spontaneously and proliferation was further enhanced in two patients by rTNF-alpha. TNF binding assays gave a value of approximately 390 to 1,400 binding sites/cell for TNF and a dissociation constant (kd) of approximately 60 pmol/L. These data indicate that rTNF-alpha, in contrast to its cytotoxic/cytostatic effects, can also induce proliferation of tumor cells.
The bcr gene in Philadelphia chromosome positive acute lymphoblastic leukemia
Authors: Heisterkamp N , Jenkins R , Thibodeau S , Testa JR , Weinberg K , Groffen J 
Published: October 2019

Abstract
In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph′) chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph′-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph′-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph′-translocation. Within the group of Ph′-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL.
Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3′ end of the BCR gene first intron
Authors: Chen SJ , Chen Z , Hillion J , Grausz D , Loiseau P , Flandrin G , Berger R 
Published: October 2019

Abstract
About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M- BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8- kb region of the first intron of the BCR gene (called bcr2 or m-BCR-1). In this report we examined two cases of Ph1 acute lymphoblastic leukemia in adult patients that exhibited breakpoints in a 5-kb segment of the BCR gene first intron, 16 kb upstream of the previously described cluster, suggesting the possibility of a second minor breakpoint cluster. In addition, the breakpoints on chromosome 9 were located in a region just 5′ of the c-abl exon la.
Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes
Authors: Wiley JS , Dubyak GR 
Published: October 2019

Abstract
Extracellular adenosine triphosphate (ATP) is known to reversibly increase the cation permeability of a variety of freshly isolated and cultured cell types. In this study the effects of extracellular ATP were studied using peripheral blood lymphocytes (PBL) isolated from both normal subjects and from patients with chronic lymphocytic leukemia (CLL). Changes in the permeability to Na+, Rb+, and Li+ ions were measured using conventional isotope and flame photometry techniques. In addition, changes in cytosolic (Ca2+) were fluorimetrically monitored to assess possible changes in net Ca2+ influx. ATP produced a 12-fold increase in 22Na+ influx into CLL cells but only a 3.5-fold increase in this flux in PBL cells. A maximal response was produced by 0.1 mmol/L ATP in the absence of Mg2+, while a twofold molar excess of Mg2+ over ATP abolished the response. ATP had no effect on the passive (ouabain-insensitive) 86Rb+ influx into PBL cells but stimulated this flux by fivefold in the CLL cells. Li+ influx into CLL cells was also stimulated threefold by ATP. Under these same conditions ATP also produced a net increase in total cell Na and a decrease in total cell K in the CLL cells. Exclusion of two normally impermeable dyes, trypan blue and ethidium bromide, was not altered in the ATP-treated CLL cells. Finally, extracellular ATP (3 mmol/L) produced no significant change in the cytosolic (Ca2+) of normal, monocyte-depleted populations of PBL. Conversely, this same concentration of ATP produced a very rapid (complete within 30 seconds) and a significant (an average threefold peak change) increase in the cytosolic (Ca2+) of cell preparations derived from five out of nine CLL patients. In these latter CLL cells, the ATP-induced elevation in cytosolic (Ca2+) appeared to be due to a net increase in Ca2+ influx, since no elevations were observed when the extracellular (Ca2+) was reduced to less than 0.1 mmol/L. These actions of ATP were specific in that equimolar concentrations of other nucleotides were without effect. These data indicate that treatment of CLL lymphocytes with extracellular ATP4 produces large increases in cation permeability. In contrast, there is less or no ATP-induced permeabilization of normal PBL.
Expression of protooncogene c-myb in normal human hematopoietic cells
Authors: Kastan MB , Slamon DJ , Civin CI 
Published: October 2019

Abstract
Expression of the protooncogene, c-myb, in various subpopulations of normal human hematopoietic cells was characterized. Cells expressing the immature cell surface marker, CD34 (My10), were isolated by immune adherence with the “panning” technique or immunomagnetic microspheres and were shown to be strongly positive for c-myb protein expression in an immunoperoxidase assay. The CD34+ progenitor cell population was further separated into myeloid plus erythroid progenitors (CD34+, CD10- ) v B-lymphoid precursors (coexpressing CD34 and CD10) by two-color FACS. Both CD34+ progenitor cell subsets strongly expressed c-myb protein by the immunoperoxidase assay. A flow cytometric assay was then developed which permitted simultaneous detection of a cell-surface antigen (to characterize lineage and stage of maturation) and the nuclear oncoprotein. This assay confirmed that CD34+ cells were strongly positive for c-myb expression and also allowed quantitative comparisons of c-myb expression in selected populations of other normal hematopoietic cells. Most human bone marrow cells appear to express some level of c-myb protein, although the CD34+ progenitor cell population expresses the highest amount.
Myelostimulatory activity of recombinant human interleukin-2 in mice
Authors: Talmadge JE , Schneider M , Keller J , Ruscetti F , Longo D , Pennington R , Bowersox O , Tribble H 
Published: October 2019

Abstract
In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy.