Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal lymphoid cells contain glucocorticoid receptor. A variety of stimuli that activate these cells also induce increases in receptor concentration. Similar glucocorticoid receptors can be detected in lymphoid cells from patients with acute lymphoblastic leukemia (ALL). Absence of the glucocorticoid receptor (usually found in treated patients) predicts lack of glucocorticoid responsiveness. Furthermore, in our hands, glucocorticoid receptor levels correlate with the duration of complete remission in ALL (though not in other forms of leukemia). This association is independent of cell type, age, sex, or initial leukocyte count. The level of receptor shows a negative correlation with increasing aggressiveness of the tumor (null-cell leukemia greater than T-cell leukemia greater than Burkitt's lymphoma).
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PMID:Clinical implications of glucocorticoid receptors in human leukemia. 695 40

In this study we describe the morphologic and immunohistochemical evaluation of bone marrow biopsies from 14 patients with therapy-related myelodysplastic syndromes (t-MDS). We employed CD34, anti-HLA-Dr, anti-elastase, CD68, anti-glycophorin, CD61 monoclonal antibodies immunostaining, and enzyme histochemistry for chloroacetate esterase. Moreover, we used PC10, a MAb raised against the proliferating cell nuclear antigen, to study the proliferative capacity of these marrows. Our data suggest that diagnosis of refractory anemia with excess of blasts (versus chronic myelomonocytic leukemia), the abnormal localization of immature precursors, marrow fibrosis, and augmented CD34 expression in the bone marrow biopsy are ominous prognostic factors at a statistically significant level (p < 0.0005). A combined morpho-immunohistochemical analysis of bone marrow biopsy correctly classifies t-MDS cases according to the biologic and clinical aggressiveness.
Leukemia 1993 Jun
PMID:Therapy-related myelodysplastic syndromes: FAB classification, bone marrow histology, and immunohistology in the prognostic assessment. 768 97

To clarify the clinical and biological significance of beta 2-microglobulin (beta 2-M) in serum of adult T cell leukemia (ATL) associated with human lymphotropic virus type-I (HTLV-I), beta 2-M was measured in 52 patients with ATL (acute ATL, 35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smoldering ATL, three patients), and it was compared with serum lactic dehydrogenase (LDH). Statistical analysis disclosed a correlation between beta 2-M level and the percentage of abnormal lymphocytes (P < 0.05) and platelet count (P < 0.01). There was a correlation between LDH and platelet count (P < 0.01), and a tendency of correlation between LDH and the percentage of abnormal lymphocytes (P < 0.15). Significant difference was present in beta 2-M as well as LDH between acute ATL and chronic ATL (P < 0.01), and between acute ATL and smoldering ATL (P < 0.01). We also investigated a significant inverse correlation between beta 2-M level as well as LDH level and the length of survival after the initial diagnosis (P < 0.01). Thus, the beta 2-M level may indicate the aggressiveness of ATL cells and predict the length of survival.
Leukemia 1995 Apr
PMID:Clinical significance of beta 2-microglobulin in serum of adult T cell leukemia. 772 90

To clarify the clinical and biological significance of serum thymidine kinase (TK) in adult T-cell leukaemia (ATL) associated with human lymphotropic virus type-I (HTLV-I) and in acute myeloid leukaemia (AML), TK was measured in 52 patients with ATL (acute ATL, 35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smouldering ATL, three patients), and in 27 patients with AML (one FAB MO, one M1, 10 M2, seven M3, five M4, one M5, one M6, one MU). In ATL patients, statistical analysis disclosed a close correlation between TK level and the leucocyte count (P < 0.01), and absolute number of abnormal lymphocytes (P < 0.01). However, no correlation was observed between serum lactic dehydrogenase (LDH) level and these items. Concerning the therapeutic response, a statistical difference was present in TK between complete remission and no response (P < 0.05), but not in LDH. We also investigated a significant inverse correlation between TK level as well as LDH level and the length of survival after the initial diagnosis (P < 0.01). In AML patients a close correlation of TK level with the count of leucocytes (P < 0.01), percentage of blasts in the blood (P < 0.05), therapeutic response (P < 0.01) and the length of survival after the initial diagnosis (P < 0.05) was present. Therefore the TK level may indicate the aggressiveness of leukaemic cells and predict the response to the chemotherapy and the length of survival in ATL and AML.
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PMID:Clinical significance of serum thymidine kinase in adult T-cell leukaemia and acute myeloid leukaemia. 778 70

By genetically manipulating hematopoietic cells of the myeloid lineage, including both normal cells and differentiation inducible leukemic cell lines, evidence was obtained to indicate that myeloid differentiation primary response (MyD) genes and proto-oncogenes, which are known to control cell growth, function as positive and negative regulators of terminal hematopoietic cell differentiation, which is associated with inhibition of cell growth, and, ultimately programmed cell death (apoptosis). Interferon regulatory factor-1 (IRF-1), an MyD gene induced by Interleukin 6 (IL-6) or Leukemia Inhibitory factor (LIF), plays a role in growth inhibition associated with terminal differentiation. Leucine zipper transcription factors of the fos/jun family, also identified as MyD genes, function as positive regulators of hematopoietic cell differentiation, increasing the propensity of myeloblastic leukemia cells to be induced for differentiation in vitro, and reducing the aggressiveness of their leukemic phenotype in vivo. The zinc finger transcription factor EGR-1, an MyD gene specifically induced upon macrophage differentiation, was shown to be essential for and to restrict differentiation along the macrophage lineage. Finally, evidence has been accumulating to indicate that the novel MyD genes--MyD116, MyD118 and gadd45 (a member in the MyD118 gene family)--play a role in growth arrest and apoptosis of hematopoietic cells, as well as other cell types. The proto-oncogenes c-myc and c-myb, known to regulate cellular growth, were shown to function as negative regulators of terminal differentiation. Both c-myc and c-myb are normally expressed in proliferating myeloblasts and suppressed following induction of differentiation. Deregulated and continuous expression of c-myc was shown to block terminal myeloid differentiation at an intermediate stage in the progression from immature blasts to mature macrophages, whereas deregulated and continuous expression of c-myb blocked the terminal differentiation program at the immature myeloblast stage. By manipulating myc function in conditional (differentiation inducible) mutant myeloblastic leukemia cell lines, expressing a chimeric mycer transgene, it was shown that there is a window during myeloid differentiation, after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, and where activation of c-myc has no apparent effect on mature macrophages. These myeloblastic leukemia cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal hematopoiesis and in leukemogenesis, while also providing a strategy to clone myc target genes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. 795 Oct 3

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereas fos was shown to dimerize only with juns. After birth, hematopoietic cells of the myeloid lineage, and some other terminally differentiated cell types, express high levels of c-fos. Still, the role of fos/jun transcription factors in normal myelopoiesis or in leukemogenesis has not been established. Recently, c-jun, junB, and junD were identified as myeloid differentiation primary response genes stably expressed following induction of terminal differentiation of myeloblastic leukemia M1 cells. Intriguingly, c-fos, though induced during normal myelopoiesis, was not induced upon M1 differentiation. To gain further insights into the role of fos/jun in normal myelopoiesis and leukemogenicity, M1fos and M1junB cell lines, which constitutively express c-fos and junB, respectively, were established. It was shown that enforced expression of c-fos, and to a lesser extent junB, in M1 cells results in both an increased propensity to differentiate and a reduction in the aggressiveness of the M1 leukemic phenotype. M1fos cells constitutively expressed immediate-early and late genetic markers of differentiated M1 cells. The in vitro differentiation of normal myeloblasts into mature macrophages and granulocytes, as well as the increased propensity of M1fos leukemic myeloblasts to be induced for terminal differentiation, was dramatically impaired with use of c-fos antisense oligomers in the culture media. Taken together, these observations show that the proto-oncogenes which encode for fos/jun transcription factors play important roles in promoting myeloid differentiation. The ability of the M1 leukemic myeloblasts to be induced for terminal differentiation in the absence of apparent fos expression indicates that there is some redundancy among the fos/jun family of transcription factors in promoting myeloid differentiation; however, juns alone cannot completely compensate for the lack of fos. Thus, genetic lesions affecting fos/jun expression may play a role in the development of "preleukemic" myelodysplastic syndromes and their further progression to leukemias.
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PMID:Proto-oncogenes of the fos/jun family of transcription factors are positive regulators of myeloid differentiation. 842 6

It is generally believed that relapse of acute leukemia heralds progression of the disease into a more aggressive stage. The biological behavior of leukemic cells collected from four patients with adult acute lymphoblastic leukemia (ALL) prior to treatment and at relapse was studied after engraftment into 28 unconditioned mice with severe combined immunodeficiency (SCID). Leukemic cells engrafted in all but one mouse, with major differences observed in the growth and aggressiveness of the leukemias. Recipient mice of cells derived from all patients at relapse died more rapidly in overt leukemia than those which were injected with cells obtained prior to induction treatment (P=0.0002). SCID mice that received cells from one patient at the time of diagnosis also died in terminal leukemia. Other SCID mice however, that received cells from the remaining three patients prior to treatment developed occult leukemia that was detectable in the blood or bone marrow with the use of polymerase chain reaction (PCR) or flow cytometry only. Leukemic cells recovered from mice with terminal leukemia exhibited a larger proliferating fraction than cells originally injected (P=0.004). Our results demonstrate, that during the evolution from initial presentation to relapse, ALL cells may acquire biological properties which render them more aggressive in SCID mice.
Leukemia 1996 Mar
PMID:Acute lymphoblastic leukemias from relapse engraft more rapidly in SCID mice. 864 75

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease of the elderly which can present in one of three stages; benign, intermediate or advanced. The molecular events governing the progression of CLL are poorly understood. In order to develop model systems for predicting the aggressiveness of leukemic clones in CLL, in vivo transplantation of SCID mice with CLL cells, and the in vitro growth of CLL cells on mouse and human stromal layers, were investigated. Bone marrow or peripheral blood cells from 40 patients at different stages of CLL were transplanted into 172 immune-deficient SCID mice. Thirty-five percent of SCID mice injected with CLL cells were positive for the presence of human DNA by Southern blot or PCR analysis. The most frequently involved sites were the spleen, lung, kidney and bone marrow, at levels corresponding from 0.1 to 10 percent human DNA. Thrice-weekly intraperitoneal injections of IL-2, alone or in combination with IL-7, did not increase the level of human cell engraftment. SCID mice developed endogenous thymic lymphomas at an incidence of 10-33 percent, a rate that was not increased by CLL cell transplantation. In vitro, CLL cells were able to proliferate for 9 weeks on human stromal layers supplemented with CM (conditioned media from a culture of the human bladder carcinoma cell line 5637), but failed to thrive on the murine stromal cell line MTE cultured either in CM or autologous serum. FACS analysis revealed that 81 percent of proliferating cells on human stromal layers carried the CD5 cell surface marker, identifying them as CLL cells. Previously EBV-negative CLL cells became EBV-positive after 9 to 12 weeks in culture. The results of this study provide a firm foundation for the development of in vivo and in vitro model systems for the study of human CLL.
Leukemia 1996 Aug
PMID:Engraftment of human chronic lymphocytic leukemia cells in SCID mice: in vivo and in vitro studies. 870 47

The CDKN2 gene, encoding the cyclin-dependent kinase-4 inhibitor p16, is a putative tumour-suppressor gene because it is frequently altered in many malignant tumours. We analysed the CDKN2 gene in 44 cases of adult T-cell leukaemia (ATL) by Southern blot analysis, polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing. Southern blot analysis detected a homozygous deletion of the CDKN2 gene in 5/44 patients (11.4%). Mutational analysis by the PCR-SSCP method and direct sequencing showed one nonsense mutation at codon 72 (nucleotide 232), and two missense mutations at codon 43 (nucleotide 146) and codon 97 (nucleotide 309, 3/44, 6.8%). Therefore we found changes in the CDKN2 gene, including point mutations, in 18.2% of the patients with ATL. Interestingly, most of these patients had acute type ATL. Our results suggest that the CDKN2 gene is inactivated not only by homozygous deletion but also by point mutation, and these alterations contribute to the aggressiveness of ATL.
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PMID:The CDKN2 gene alterations in various types of adult T-cell leukaemia. 882 90

The authors describe a case of cutaneous neuroendocrine (Merkell cell) carcinoma in a patient previously treated for Chronic Lymphocytic Leukaemia (CLL). The authors discuss some of the mechanisms concerning the increased frequency of a second tumour in patients with CLL and focus attention on the high incidence in CLL of secondary tumours, especially skin tumours, of which Merkell cell carcinoma is a rare example. The authors consider the possible therapeutic approaches, reported in the literature, for the treatment of this particular skin carcinoma, which on account of its aggressiveness and the preexistence of a leukaemic process requires a particularly careful therapeutic approach.
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PMID:Association between chronic lymphocytic leukaemia and secondary tumours: unusual occurrence of a neuroendocrine (Merkell cell) carcinoma. 944 93


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