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)

The case is reported of a 45 year old woman with the rare leukaemia of natural killer cell large granular lymphocyte (NK/ LGL) type. Cytometric analysis of leukaemic blasts showed that they were positive for CD2, CD38, and CD56 antigens but negative for a series of antigens including CD3, CD7, CD16, and HLA-DR. Rearrangements of the beta T cell receptor, and heavy and kappa immunoglobulin genes were not detected and neither were chromosomal abnormalities. Leukaemic blasts developed NK cytotoxicity. The patient failed to respond to aggressive chemotherapy and died three months after diagnosis. The lack of expression of HLA-DR is an extraordinary characteristic of this case, as all cases of acute NK cell leukaemias described to date expressed HLA-DR. The immunophenotype observed in the NK cell leukaemic blasts may represent the counterpart of a hypothetical normal cell precursor in an early stage of ontogenic NK cell development.
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PMID:Leukaemia of natural killer cell large granular lymphocyte type with HLA-DR-CD16-CD56bright+ phenotype. 903 41

The Wilms tumor suppressor gene (WT1) is mutated in a number of cases of Wilms' tumor as well as in mesothelioma and leukemia. It encodes a transcription factor derived from any one of four alternate transcripts. WT1 has a restricted pattern of expression within the body and within the hemopoietic system its expression is limited to primitive leukemias and a number of leukemic cell lines. Given the overexpression of WT1 in leukemias, we have addressed the question of whether this gene is expressed within the normal hemopoietic system. Mononuclear bone marrow (BM) cells obtained from normal donors were separated by fluorescence-activated cell sorting (FACS) into "primitive" (CD34+) and "mature" (CD34-) cell populations. Total RNA extracted from these cells was subjected to reverse transcriptase polymerase chain reaction (RT-PCR) using primers based on the WT1 sequence, to examine the expression of this gene within the hemopoietic system. Phenotypic purity of cells was guaranteed by performing single-cell sorting followed by RT-PCR to define the precise cellular phenotypes that express WT1. Expression of WT1 was detected in cells bearing the CD34+ phenotype but not in those cells lacking expression of CD34. In addition, single-cell analysis revealed that expression of WT1 occurred in the candidate stem cell-containing population of hemopoietic cells which have the phenotype CD34+ CD38-. Moreover, the single-cell RT-PCR analysis also demonstrated that differential expression of alternate transcripts of WT1 occurs between hemopoietic progenitor cells with the same phenotype. In conclusion, expression of WT1 is limited to early progenitors of the blood system, which suggests that this gene plays a critical role in hemopoietic development.
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PMID:Expression of the Wilms' tumor gene (WT1) in normal hemopoiesis. 940 89

Human leukocyte antigen CD38, a 45-kD single-chain, transmembrane glycoprotein, is a bifunctional ectoenzyme that participates in signal transduction pathways involved in the regulation of cell growth and differentiation. In this study, we demonstrate the nature of retinoid receptors involved in retinoic acid-induced expression of CD38 protein in the human myeloblastic leukemia cell line HL-60. We used a variant HL-60 cell line, HL-60R, in which retinoid receptor function has been abrogated by a trans-dominant negative mutation. We introduced the normal retinoic acid receptors (RAR)-alpha, -beta, and -gamma or retinoid X receptor (RXR)-alpha into HL-60R cells by retroviral vector-mediated gene transfer. Based on experiments using these cell lines and receptor-specific synthetic retinoids that preferentially bind to one of the RARs or RXRs, we conclude that RAR-alpha is involved in retinoid-induced CD38 expression in HL-60 cells. Further evidence included our demonstration that blocking of RAR-alpha with the antagonist Ro 41-5253 completely suppressed the retinoid-induced expression of CD38 mRNA transcript and the production of CD38 protein in HL-60 cells. Various tissues from transgenic mice that expressed an antisense construct of RAR-alpha lacked or produced very low levels of CD38. As expected, the tissues from transgenic mice contained 50% to 80% reduced levels of RAR-alpha. These results suggest that regulation of CD38 expression, both in vitro and in vivo, is under the direct control of RAR-alpha retinoid receptors.
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PMID:Involvement of retinoic acid receptor-alpha-mediated signaling pathway in induction of CD38 cell-surface antigen. 916 Jun 65

It has been supposed in de novo AML that malignant transformation occurs at the level of committed progenitors. Recent data of our group and others provide evidence that in AML malignant transformation may regularly occur at the level of stem cells. These cells can be discriminated by function and specific surface molecules. CD34, a glycophosphoprotein, is a cellular surface antigen characteristically expressed by stem cells. CD34+ stem cells can be further subdivided by the expression of additional surface molecules like CD38 and CD117. In this article we present results from cytogenetic examinations of FACS-isolated stem cell subpopulations in eight patients (four AML and four MDS). Six of them displayed clonal karyotype abnormalities at the time of first diagnoses in the native bone marrow (5q-; 5q- and complex abnormalities; +8; inv(16) and +8; i(17q) and -21; i(21q)). We used CD117, the receptor for the stem cell factor (also KIT oncogene) as a new cellular surface marker. CD34+/CD117+/- stem cell subpopulations were examined in two patients with AML and three patients with MDS. We found leukemic stem cells in every type of stem cell subpopulation examined (CD34+/CD38-, CD34+/CD38+, CD34+/CD117-, CD34+/CD117+). Secondary, progression-associated chromosome abnormalities likewise were demonstrable in CD34+ cells. In three patients a mosaic of normal and abnormal metaphases was found in the highly purified stem cell subpopulations. We conclude that in AML and MDS stem cells are the target of leukemogenic genetic defects. CD117 as a new marker to isolate different CD34+ subpopulations was not sufficient to discriminate between normal and leukemic stem cells. Our findings have implications for autologous stem cell transplantation, high-dose chemotherapy and the pathogenetic concept of leukemogenesis.
Leukemia 1997 May
PMID:Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117. 918 Feb 91

We established a factor-independent acute myeloid leukemia cell line, designated Ei501. The line has been growing in RPMI 1640 media for 18 months and can be maintained without addition of growth factors. Ei501 is positive for myeloperoxidase and negative for esterase and PAS. Cytogenetic analysis revealed the FAB M3 associated t(15;17) translocation and a translocation of the chromosomes 7 and 8: 46 XX, -7, +t(7;8)(q32;q13), t(15;17)(q22;q12). This karyotype was confirmed by fluorescence in situ hybridization. Ei501 cells express AML-associated surface markers such as CD13, CD33 and CD38. Although 42% of the patient's blast cells were CD34-positive, the line lacks surface expression of CD34. Furthermore the line has a number of characteristics which are detectable in blasts from AML patients, such as surface adhesion molecules, cytokines such as TGF-beta, cytokine receptors such as the IL-2 receptor beta and gamma chains or the IL-4 receptor and the genes for the transcription factor wt-1 (Wilms' tumor gene) and for the proto-oncogene bcl-2, both shown to be present in the majority of patients with AML. Additionally the line can be used as target in cytotoxicity assays using IL-2 activated cytotoxic lymphocytes as effector cells. In conclusion, besides a rare karyotype the Ei501 cell line has several features common in AML, and may therefore be used as a model to study pathogenetic mechanisms in acute myeloid leukemia.
Leukemia 1997 May
PMID:Establishment and characterization of a new, factor-independent acute myeloid leukemia line designated Ei501. 918 Feb 96

Four paroxysmal nocturnal hemoglobinuria (PNH) patients with severe thrombocytopenia, hemolytic anemia and neutropenia were treated using a combination of filgrastim (G-CSF) and cyclosporin. In all patients a trilineage response of hematopoiesis was achieved. In addition, the proportion of glycosyl-phosphatidylinositol (GPI)-deficient granulocytes decreased. All patients mobilized CD34+ hematopoietic progenitors into peripheral blood after starting treatment with G-CSF. The majority of early progenitors (CD34+ CD38-) after mobilization into peripheral blood was found to be unaffected by the GPI-anchoring defect. No patient developed leukemia while under therapy. We conclude from these data that the combination of G-CSF and cyclosporin represents an efficient option for the treatment of hypoplastic PNH.
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PMID:G-CSF and cyclosporin induce an increase of normal cells in hypoplastic paroxysmal nocturnal hemoglobinuria. 920 Sep 95

We have identified ten patients with acute myeloid leukemia (AML) and one patient with chronic myeloid leukemia with megakaryocytic crisis who displayed an inv(3)(q21q26). Seven of them had an additional monosomy 7. Most of them had a myelodysplastic syndrome (MDS) preceding AML, normal or increased platelet counts, increased number of megakaryocyte, megakaryocytic dysplasia, and erythroid dysplasia. There was a high incidence of resistance to induction chemotherapy, short remission time, and early relapse. Seven patients were immunologically analyzed. The main immunophenotypes were as follow: CD7+, CD34+, HLA-DR+, CD38+, CD13+, CD33+, CDw65+, CD2-, CD3-, CD4-, CD8-, CD19+, CD20-, CD11b-. Our results suggest that the leukemia with inv(3)(q21q26) represents a new cytogenetic-clinicopathologic subtype, characterized by 1) abnormal megakaryopoiesis and multiple hematopoietic lineage involvement; 2) an antecedent MDS; 3) poor response to conventional chemotherapy; and 4) expression of CD7, CD34, CD38, HLA-DR, CD13, and CD33 antigens. We propose that the malignant transformation in patients with inv(3)(q21q26) occurs in an early stem cell prior to lineage commitment.
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PMID:Chromosomal abnormality inv(3)(q21q26) associated with multilineage hematopoietic progenitor cells in hematopoietic malignancies. 920 72

On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.
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PMID:Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. 921 98

We describe the clinical and laboratory features of an unusual case with Sezary cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly. There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine showed diffuse infiltration by atypical lymphoid cells. By ultrastructural analysis the cells were small to medium-size lymphocytes with nuclear features identical to Sezary cells. Immunophenotyping showed that most peripheral blood mononuclear cells were negative with B lymphoid, myeloid, and stem cell-associated markers and were also negative with most T lymphoid markers (CD2, CD4, membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38 (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal rearrangement of the TCR beta and gamma chain genes. The patient was initially treated with vincristine, doxorubicin and asparaginase and then with six cycles of CHOP, achieving a complete remission and remaining free of disease 22 months from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell-like leukemia, in which cells lacked most of the T cell-associated antigens.
Leukemia 1997 Aug
PMID:Sezary cell-like leukemia with atypical immunophenotype. 926 98

The ability of retinoids to regulate interleukin-2 receptor (IL-2R) levels on human T-cells may play a fundamental role in the immunomodulating effects of these compounds. As a cell line model for studying this phenomenon, we tested the effects of retinoic acid (RA) on the expression of IL-2Ralpha and IL-2Rbeta in Hut78 cells, a mature T-cell line derived from a Sezary T-cell leukemia. Our results demonstrated 4- to 20-fold increases in the surface expression and mRNA levels of both of these receptor components at RA concentrations starting at 10(-10) M with maximal induction at 1 microM RA. RA-induced upregulation of IL-2Rbeta was found to be transcriptionally mediated in a protein-synthesis-independent fashion; however, activation of the IL-2Rbeta promoter could not be demonstrated in transient transfection experiments utilizing reporter gene constructs containing all currently known regulatory elements of the IL-2Rbeta promoter. Enhancement of IL-2Ralpha/beta by RA was accompanied by upregulation of the expression of CD38, CD69, CD45RO, and HLA-DR, surface molecules known to be associated with T-cell activation. Parallel effects were induced by RA on T-blasts generated from primary human lymphocytes suggesting the physiologic relevance of the Hut78 cell line model. Taken together, our findings demonstrate the ability of RA to upregulate IL-2R expression and enhance the activation state of Hut78 cells. The dramatic enhancing ability of RA on IL-2Rbeta expression does not appear to be mediated through interaction with currently defined regions of the IL-2Rbeta promoter.
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PMID:Retinoid regulation of interleukin-2 receptors on human T-cells. 926 95


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