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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper presents an analysis of glutathione S-transferase (GST) activity of leukemic cells in 30 patients with acute leukemias and its predictive value for therapy. Blast cells were isolated from peripheral blood or bone marrow before induction therapy using Ficoll density gradient. GST activity was measured according to the spectrophotometric assay based on the use of 1-chloro-2,4-dinitrobenzene as a substrate. The results did not show any significant differences between activities of the enzyme within the different leukemia types according to the French-American-British (FAB) classification. The patients who achieved complete remission demonstrated the lowest value of enzyme activity. The highest enzyme activity was observed in those patients who achieved partial remission and the non-responsive patients presented a GST value within the median of these two groups. Two categories of patients were represented within the non-responsive treatment group. One was resistant to the conventional therapy and in the other death was caused by infectious or hemorrhagic complications. The mean GST activity in these two groups of patients differ greatly. These results suggest that low GST activity of leukemic cells could be a favourable prognostic factor whereas high GST values could help to find out the group of patients who should be further analysed prior to induction therapy.
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PMID:Glutathione S-transferase activity of leukemic cells as a prognostic factor for response to chemotherapy in acute leukemias. 204 80

We studied the organization of immunoglobulin (Ig) genes and the beta-chain gene of the T cell receptor (TCR) along with the clinical features, immunophenotypes, and karyotypes of 14 children with acute leukemia at diagnosis and relapse. The median time to relapse was 23 months. Eleven children had identical gene rearrangement patterns at diagnosis and relapse. All three patients whose blast cells showed variations in gene rearrangement patterns between diagnosis and relapase also demonstrated a change in the immunophenotype: one from cALLA+ to cALLA- B precursor cell ALL; one from T-ALL to AML; and one showed a marked increase in myeloid characteristics at relapse. Blast cells from these three patients at relapse showed the presence of chromosomal translocations involving 11q23; for two patients, this involved replacement of the original karyotype. We conclude that while most relapses are the result of reemergence of the original clone, new clones that differ in immunophenotype, karyotype, and gene rearrangement are occasionally present at relapse. Relapses may also occur in which the original clone has undergone major changes in gene expression and arrangement of the Ig heavy chain genes in the absence of karyotypic replacement.
Leukemia 1990 Nov
PMID:Alterations in immunoglobulin or T cell receptor gene rearrangement at relapse: involvement of 11q23 and changes in immunophenotype. 217 64

In the present study the effects of a combined treatment with cytosine-arabinoside (Ara-C) and interleukin-3 (IL-3) on acute myeloblastic leukaemia clonogenic cells and on normal haemopoietic progenitors was investigated, with the aim of improving the tumoricidal effect of cycle specific drugs. Blast cells from 24 acute myeloblastic leukaemia (AML) patients were screened with a short-term proliferative assay based on 3H-thymidine (3H-TdR) uptake for their response to IL-3. To evaluate the synergism between the growth factor and Ara-C, the cells were pretreated for 3 d in liquid culture in the presence or absence of IL-3 (10 U/ml) and for the last 24 h with Ara-C (3 micrograms/ml). The cells were then washed and seeded in semisolid media to assess their clonogenic ability. The results showed that, in those cases which were good responders to IL-3 in the 3H-TdR uptake assay (19 out of 24), Ara-C exposure eliminated a greater proportion of clonogenic cells if pretreated with IL-3 than if untreated (P less than 0.001), while in cases unresponsive to IL-3 this effect was not significant. Moreover, when the same protocol was applied to bone marrow cells from normal donors, it was found that IL-3 pretreatment did not significantly enhance the toxic effect of Ara-C on day 14 granulocyte-macrophage colony forming units (CFU-GM) and erythroid burst forming units (BFU-E). Finally IL-3 pretreatment was also able to increase the cytotoxic effect of Ara-C on leukaemic cells co-cultured, to simulate clinical AML remission, with normal bone marrow cells. The results indicate that IL-3 may improve the therapeutic index of cycle-specific drugs in AML therapy.
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PMID:Different sensitivity of normal and leukaemic progenitor cells to Ara-C and IL-3 combined treatment. 222 44

A case of acute megakaryoblastic leukemia with complex chromosomal aberrations is reported. A 63-year-old man was admitted to our hospital because of pancytopenia. Bone marrow aspiration resulted in a dry tap and biopsy showed hypoplastic marrow with fibrosis. Blast cells in the peripheral blood were identified as megakaryoblasts because they were positive for electron microscopic platelet peroxidase (PPO). In addition, monoclonal antibody, TP80, to platelet glycoprotein II b-III a reacted with in about 26% of the blast cells. Chromosomal analysis of the peripheral blood revealed a mosaic pattern of a normal karyotype and abnormal ones, including 44, XY, -5, -7, -18, 10q-, +marker.
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PMID:[Acute megakaryoblastic leukemia with complex chromosomal aberrations]. 228 68

We applied the MTT dye reduction assay to the anti-cancer drug sensitivity test using short-term microplate cultures. Blast cells were cultured with approximately 25 anti-cancer drugs for 4 days. After cultivation, MTT dye was placed in each well, and the formazans generated by living cells were dissolved in acidified isopropyl alcohol. The absorbance of each well was measured at a scanning microplate photometer. When we made the table of the cytotoxicity index (CI) that was classified into anti-cancer drugs and concentrations for each leukemic sample, it was possible to compare efficacy with different drugs and to select the effective ones. Retrospectively, the in vitro results were compared with the clinical responses of the 34 patients (26 of acute lymphocytic leukemia [ALL] and eight of acute nonlymphoblastic leukemia [ANLL]) who were treated by combination chemotherapy. The following results were obtained: true-positive rate, 78.1%; true-negative rate, 57.1%; and predictive accuracy, 74.4%. Therefore, the MTT assay-CI table might serve as a reliable tool for the selection of effective chemotherapy in patients with acute leukemia.
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PMID:An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia. 230 78

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.
Leukemia 1990 Jan
PMID:Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials. 240 63

To evaluate the relative merits and deficiencies of Millipore filter and cytocentrifuge preparations in the detection of central nervous system (CNS) acute leukemia in pediatric patients, 300 cerebrospinal fluid (CSF) specimens from 17 patients were prepared by both methods. The 17 patients studied were all diagnosed and treated for CNS leukemia. Leukemic blast cells were found by at least one method in 91 CSF specimens, and the results of both techniques were positive in 77 (85%) of 91 specimens. Of the 14 specimens in which the results of only one method were positive, seven yielded positive results only by the cytocentrifuge method, and seven yielded positive results only by the Millipore filter method. In 12 of the 14 discrepant specimens, the paired specimen whose results were not interpreted as positive was technically unsatisfactory (nine specimens) or had cells suspicious for blast cells rather than unequivocal blast cells (three specimens). Blast cells were identified in specimens with low nucleated cell counts (less than or equal to 5/mm3) by both methods and usually were immediately preceded or followed by CSF specimens showing florid disease. We conclude that performance of both methods is unnecessary for routine surveillance if processing techniques yield quality preparations. Cytocentrifuge preparations stained by Wright's method allow better morphologic correlation with bone marrow blast cells and allow easier identification of blood or bone marrow contamination.
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PMID:Millipore filter vs cytocentrifuge for detection of childhood central nervous system leukemia. 242 76

We have established an in vitro system with which to examine the ability of Abelson murine leukemia virus (A-MuLV) to infect early hemopoietic progenitor cells. Blast cell colonies containing less than 100 cells were shown to contain up to 85% of cells with secondary hemopoietic colony-forming ability. Infection of cells from these blast colonies resulted in generation of transformed mast cell lines when a feeder was provided. Morphological examination of cells taken from infected cultures at various times postinfection indicated a progression of cellular differentiation to the mast cell lineage. Southern analysis on early subclones of transformed cells from two wells, using a v-abl specific probe, indicated a unique pattern of viral integration amongst subclones, suggesting that all subclones had derived from a single cell in each well. Similar results were observed with helper-free Abelson virus obtained by transfecting psi 2 cells with P160 A-MuLV proviral DNA. These data indicate that hemopoietic progenitor cells can be infected by A-MuLV and subsequently in our in vitro culture condition give rise to transformed mast cell lines.
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PMID:Blast colonies containing hemopoietic progenitor cells can give rise to Abelson virus (A-MuLV)-transformed cell lines. 244

The blast cells of acute myeloblastic leukemia may be considered as a renewal population maintained by stem cells that are capable of both self-renewal and differentiation. Blast stem cells grow in culture usually when stimulated by growth factors normally active on myelopoietic cells. Two culture methods permit an evaluation of the balance between self-renewal and differentiation; previous studies have shown that this balance can be affected by recombinant growth factors. These include interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF), active on early cells in normal myelopoiesis, and G-CSF and CSF-1, restricted in normal hemopoiesis to the granulopoietic and macrophage/monocytic lineages, respectively. In this paper we report the results of evaluating the effects on these recombinant growth factors alone or in mixtures of two at optimal concentrations. The results were obtained either using titrations of colony formation in methylcellulose or growth in suspension. Star diagrams, a technique from exploratory data analysis, were used to provide quantitative and graphic displays of the results of the recombinant factors on the balance between blast self-renewal and differentiation. Blasts from 4 acute myeloblastic leukemia patients and one patient with the blast crisis of chronic myeloblastic leukemia were examined in detail. The great patient-to-patient variation usually observed was seen in both plating efficiency in methylcellulose and growth pattern in suspension. In spite of this variation, a common pattern of response to growth factors emerged. When the early acting factors, IL-3 and GM-CSF, were combined, the effect was quantitatively and qualitatively similar to the largest stimulation seen with either of the factors alone. In contrast, late-acting factors, G-CSF and CSF-1, influenced each other's effects when present together and each affected the activities of GM-CSF and IL-3. Notably, CSF-1, which often led to the accumulation of adherent, terminal cells in suspension, usually maintained or increased this differentiation-like activity in combination. G-CSF also favored differentiation in combination, although the effect was usually to increase the number of colonies in methylcellulose, most of which consist of blast cells incapable of further divisions. The results are discussed as they relate to the postulated structure of the blast population and the normal targets of the recombinant growth factors.
Leukemia 1988 Jun
PMID:The effects of combinations of the recombinant growth factors GM-CSF, G-CSF, IL-3, and CSF-1 on leukemic blast cells in suspension culture. 245 60

The effects of transforming growth factor-beta (TGF-beta) on the blast progenitors from nine acute myeloblastic leukemia patients were studied in methylcellulose and suspension cultures. Leukemic blast progenitors undergo terminal divisions with a limited differentiation in methylcellulose culture, making blast colonies. Blast progenitors can renew themselves. The self-renewal can be reflected by secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the exponential growth of clonogenic cells in suspension culture. TGF-beta suppressed primary and secondary colony-formation in methylcellulose culture. Furthermore, TGF-beta suppressed the recovery of clonogenic cells in suspension. The results indicate that TGF-beta is effective in inhibiting not only terminal divisions but also self-renewal of leukemic blast progenitors.
Leukemia 1989 Aug
PMID:Inhibition of the in vitro growth of blast progenitors from acute myeloblastic leukemia patients by transforming growth factor-beta (TGF-beta). 247 59


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