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)

Type 2 dendritic cell (DC2) acute leukemia has been recently described. We report here an unusual case of a 17-yr-old adolescent with overlapping features of DC2 and myeloid/NK cell precursor acute leukemia as defined by Suzuki et al. The patient presented with lymphadenopathy and hepatosplenomegaly without extranodal manifestations in skin or elsewhere. The morphologic, cytochemical and immunophenotypic features were compatible with those described in DC2 acute leukemia, with co-expression of CD4, CD56 and CD123 antigens. The novel markers BDCA-4 and BDCA-2 considered specific for DC2s were co-expressed. However, bright CD7 positivity along with a dim expression of CD33 (57%) and CD117 (27%) were also noted. Additionally, there was bright expression of NG2 monoclonal antibody 7.1, a frequent finding in myeloid/NK cell precursor acute leukemia. The interpretation of the immunophenotypic profile leads to the hypothesis on the existence of borderline cases between DC2 and myeloid/NK cell precursor acute leukemia. Still, other hypotheses can not be overlooked, such as the possibility for a kind of variant monoblastic leukemia or of another rare entity of acute unclassified leukemia.
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PMID:An unusual case of CD4+ CD7+ CD56+ acute leukemia with overlapping features of type 2 dendritic cell (DC2) and myeloid/NK cell precursor acute leukemia. 1295 Feb 40

We studied the morphologic, immunohistochemical, and clinical characteristics of 158 cases of lymphoblastic lymphoma. Based on immunophenotyping and cell lineage, cases were classified into B-cell type (CD20,CD19 or CD79a+, n = 53), T-cell type (surface CD3+, n = 84), and non-B, non-T type (B cell marker- and surface CD3-, n = 21). The latter group was further divided based on immunohistochemistry into: 1) CD7+ stem cell lymphoma (CD7+SCL) [CD4-, CD7+, CD33+/-, CD56-], 2) blastic natural killer cell lymphoma (B-NKL) [CD4-, CD7+/-, CD33-, CD56+, CD123-], 3) myeloid/NK precursor cell leukemia (M/NKL) [CD4-, CD7+, CD33+, CD56+], and 4) CD4+CD56+ hematodermic malignancy (CD4+CD56+) type [CD4+, CD7+/-, CD33-, CD56+, CD123+]. The CD7+SCL and M/NKL types frequently exhibited bone marrow invasion and mediastinal masses. All CD4+CD56+ types were associated with skin lesions. B-NKL type is included into Blastic NK lymphoma in new World Health Organization classification with CD4+CD56+ type. But the cases of B-NKL were more reminiscent of CD7+SCL or M/NKL type than the CD4+CD56+ type, both clinically and histologically. We propose that blastic NK lymphoma, a disease entity in the new WHO classification, should be divided into two types based on phenotypes and clinical features. The non-B, non-T lymphomas exhibited poorer prognoses, similar to that of B-cell lymphomas, than T-cell type tumors (P = 0.009). Among the 21 tumors, the prognosis of the four subtypes did not differ significantly; however, cases receiving aggressive chemotherapy and stem cell transplantation had a more favorable prognosis than those receiving only traditional chemotherapy and radiation therapy (P = 0.0089).
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PMID:Non-B, non-T neoplasms with lymphoblast morphology: further clarification and classification. 1516 81

Continuous human leukemia-lymphoma (LL) cell lines represent a rich resource of abundant, accessible and manipulable living cells contributing significantly to a better understanding of the pathophysiology of hematopoietic tumors. In particular, classical and molecular cytogenetics have benefitted enormously from the availability of LL cell lines with specific chromosomal abnormalities. Such aberrations may be the portal to the discovery of novel oncogene rearrangements for which positive cell lines provide a resource for both discovery and functional studies. The new continuous leukemia cell line MUTZ-11 was established in 1994 from the peripheral blood of a 60-year-old woman with acute myeloid leukemia (AML) M4 (following 2 years with myelodysplastic syndromes). DNA fingerprinting confirmed the authenticity and derivation of the cell line. The immunoprofile as determined by flow cytometry was as follows: positive for myelocytic markers (CD13, CD15, CD33, CD65 and CD68), negative for T-cell (except for CD4 and CD7), B-cell and erythroid-megakaryocytic markers. The cell line is constitutively cytokine-dependent and growth depends on externally added cytokines. With regard to cytokine receptor expression, the cell line was found to be positive for GM-CSFRalpha (granulocyte-macrophage colony-stimulating factor receptor, CD116), Kit (CD117) and IL-3Ralpha (interleukin-3 receptor, CD123). The cytokine response profiles as determined by [(3)H]-thymidine incorporation assay were: 2-to-12 fold growth stimulation of MUTZ-11 by GM-CSF, IFN-alpha (interferon), IFN-beta, IFN-gamma, IL-3 and SCF (stem cell factor); growth inhibition by TGF-beta1 (transforming growth factor), TNF-alpha (tumor necrosis factor) and TNF-beta. Cytogenetic analysis showed the following consensus karyotype: 46, XX, der(16)t(16;17)(p13.3;q23)x2. Previous molecular biological analysis documented that MUTZ-11 cells carry both an FLT3 internal tandem duplication (ITD) and an MLL partial tandem duplication (PTD). The scientific significance of MUTZ-11 lies (i). in the absolute cytokine-dependency and the proliferative response to various cytokines, (ii). in the unique cytogenetic (disomic t(16;17)) and (iii). molecular biological alterations (FLT3 ITD + MLL PTD). In summary, the new cytokine-dependent AML-derived cell line MUTZ-11 displays unique novel features and emphasizes the need for comprehensive analysis of new LL cell lines which may lead to the discovery of important pathogenetic alterations.
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PMID:New cytokine-dependent acute myeloid leukemia cell line MUTZ-11 with disomic chromosome rearrangement t(16;17). 1506 4

Early plasmacytoid dendritic cell (pDC) leukemia/lymphoma has recently been described as a CD4(+)CD56(+) lineage negative malignancy with characteristic clinical, morphologic, immunophenotypic, and biological features. We present a case of a 72-year-old man who was diagnosed with isolated skin involvement 30 months ago and received numerous chemotherapy cycles that did not prevent three relapses of the disease, the last two involving the bone marrow. The bone marrow was nearly completely infiltrated with small- to medium-sized blasts displaying a high nuclear to cytoplasmic ratio, a cytoplasm with faint basophilia lacking granulations or Auer rods. Small vacuoles surrounding the nucleus were frequently observed. Flow cytometry showed CD4(+), CD56(+), CD45(+), CD38(+), HLA-DR(+), CD33(+), CD123(+), CD2(-), cyCD3(-), CD7(-), CD10(-), CD11b(-), CD13(-), CD14(-), CD16(-), CD19(-), cyCD22(-), CD24(-), CD34(-), CD57(-), CD61(-), CD64(-), CD65(-), cyCD79a(-), CD117(-), MPO(-), and TdT(-) population. At the second bone marrow relapse, CD117 was also positive. Our patient was initially treated with acute myeloid leukemia-type chemotherapy, later he was given acute lymphoblastic leukemia-type treatment, and at the last relapse he received CHOP chemotherapy. Each treatment led to rapid response of tumor manifestations with disease-free intervals of 7 months, 9 months, and 8 months, respectively. Although patients usually have an ominous prognosis, with only 25% living more than 24 months, our patient is alive after 30+ months and has again achieved complete remission after the last chemotherapy.
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PMID:Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes. 1531 55

In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts ('AML-cuplike'). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AML-cuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AML-cuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.
Leukemia 2004 Oct
PMID:A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication. 1534 44

Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that nonobese diabetic/severe combined immunodeficiency (NOD/SCID) leukemia-initiating cells (SL-ICs) are restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from an HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing.
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PMID:Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. 1613 73

Dendritic cells (DC) as potent antigen-presenting cells (APC) and T cells as effector cells play an essential role in the pathophysiology of both graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactions after transplantation. Therefore, we determined the kinetics of DC and T-cell chimerism establishment after allogeneic hematopoietic cell transplantation (AHCT) in a group of 144 patients, using fluorescence-activated cell sorting (FACS) or magnetic cell sorting (MACS) followed by FISH or STR-PCR analysis for chimerism evaluation. In all, three cell lines investigated (CD3(+) T cells, CD11c(+) DC1 and CD123(+) DC2), we found a rapid and consistent establishment of complete donor chimerism (CDC) in over 70% of all patients during the first 6 weeks after AHCT. The rate of patients with CDC increased significantly over time within the first year after transplantation. A related donor (P=0.004) as well as an underlying lymphatic leukemia (P=0.03) were found to be significantly associated with development of MC in T cells. No significant correlation between DC or T cell chimerism and GvHD or relapse was detected. Our results thus demonstrate a fast and stable CDC in DC1, DC2 and T cells after AHCT that continuously increases over time in nearly all patients.
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PMID:Kinetics of dendritic cell chimerism and T cell chimerism in allogeneic hematopoietic stem cell recipients. 1625 29

CD4(+)/CD56(+) haematodermic neoplasm or 'early' plasmacytoid dendritic cell leukaemia/lymphoma (pDCL) was described as a disease entity in the last World Health Organisation/European Organisation for Research and Treatment of Cancer classification for cutaneous lymphomas. These leukaemia/lymphomas co-express CD4 and CD56 without any other lineage-specific markers and have been identified as arising from plasmacytoid dendritic cells. Despite a fairly homogeneous pattern of markers expressed by most pDCL, numerous distinctive features (e.g. cytological aspects and aberrant marker expression) have been reported. This may be related to the 'lineage-independent developmental' programme of dendritic cells, which may be able to develop from either immature or already committed haematopoietic progenitors. This highlights the need for specific validated markers to diagnose such aggressive leukaemia. Here, we propose--among others (e.g. T-cell leukaemia 1)--blood dendritic cell antigen-2 and high levels of CD123 expression as potential markers. In addition, we propose a multidisciplinary approach including several fields of haematology to improve pDCL diagnosis.
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PMID:Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity? 1736 8

Schizophrenia is a strongly heritable disorder, and identification of potential candidate genes has accelerated in recent years. Genomewide scans have identified multiple large linkage regions across the genome, with fine-mapping studies and other investigations of biologically plausible targets demonstrating several promising candidate genes of modest effect. The recent introduction of technological platforms for whole-genome association (WGA) studies can provide an opportunity to rapidly identify novel targets, although no WGA studies have been reported in the psychiatric literature to date. We report results of a case-control WGA study in schizophrenia, examining approximately 500 000 markers, which revealed a strong effect (P=3.7 x 10(-7)) of a novel locus (rs4129148) near the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin 3 receptor alpha) in an independent case-control cohort revealed both common intronic haplotypes and several novel, rare missense variants associated with schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia may help explain prior epidemiologic data relating the risk for this illness to altered rates of autoimmune disorders, prenatal infection and familial leukemia.
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PMID:Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. 1752 11

The specific alpha subunit of the interleukin-3 receptor (IL-3Ralpha, CD123) is strongly expressed in various leukemic blasts and leukemic stem cells and seems to be an excellent target for the therapy of leukemias. In this study, immunotoxins were developed to target CD123 only, which bypasses the dependence on other subunits to form intact IL-3R. Three anti-CD123 hybridomas (26292, 32701, and 32716) were selected on the basis of their affinity for CD123. Total RNAs were extracted from the 3 anti-CD123 hybridomas and used to clone the fragment of variable region (Fvs). The Fvs were assembled into single chain Fvs and fused to a 38-kd fragment of Pseudomonas exotoxin A to make recombinant immunotoxins. 26292(Fv)-PE38 was found to have the highest cytotoxic activity on the CD123 expressing leukemia cell line TF-1. It bound the cells with a kd of 3.5 nM. Another immunotoxin, 32716(Fv)-PE38, belonging to a different epitope group, had a similar binding ability but was less active, demonstrating the role of epitope selection in immunotoxin action. The cytotoxic activity of 26292(Fv)-PE38 was increased from 200 to about 40 ng/mL by mutating the REDLK sequence at the C terminus to KDEL. 26292(Fv)-PE38-KDEL was specifically cytotoxic to several CD123 expressing cell lines (TF-1, Molm-13, and Molm-14) with good CD123 expression but not to ML-1 or U937 with low or absent expression. In conclusion, 26292(Fv)-PE38-KDEL shows good cytotoxic activity against CD123 expressing cell lines, and merits further development for the possible treatment of acute myeloid leukemia and other CD123 expressing malignancies.
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PMID:New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells. 1766 24


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