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)

Vector-containing medium harvested from murine packaging cell lines has been shown to contain factors that can negatively influence the transduction and maintenance of hematopoietic stem cells. Thus, we generated a human packaging cell line with a gibbon ape leukemia virus pseudotype (Phoenix-GALV), and we evaluated vectors produced by Phoenix-GALV for their ability to transduce hematopoietic progenitor/stem cells. In 3 baboons, we used a competitive repopulation assay to directly compare GALV-pseudotype retrovirus vectors produced by either Phoenix-GALV or by the NIH 3T3-derived packaging cell line, PG13. In 3 additional baboons we compared Phoenix-GALV-derived vectors to more recently developed lentiviral vectors. Gene transfer efficiency into hematopoietic repopulating cells was assessed by evaluating the number of genetically modified peripheral blood and marrow cells using flow cytometry and real-time polymerase chain reaction. Transduction efficiency of hematopoietic repopulating cells was significantly higher using the Phoenix-GALV-derived vector as compared with the PG13-derived vectors or lentiviral vectors, with stable transduction levels up to 25%. We followed 2 animals for more than one year. Flow cytometric analysis of hematopoietic subpopulations in these animals revealed transgene expression in CD13(+) granulocytes, CD20(+) B lymphocytes, CD3(+) T lymphocytes, CD61(+) platelets, as well as red blood cells, indicating multilineage engraftment of cells transduced by Phoenix-GALV-pseudotype vectors. In addition, transduction of human CD34(+) cells was significantly more efficient than transduction of baboon CD34(+) cells, suggesting that Phoenix-GALV-derived oncoretroviral vectors may be even more efficient in human stem cell gene therapy applications.
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PMID:Highly efficient gene transfer into baboon marrow repopulating cells using GALV-pseudotype oncoretroviral vectors produced by human packaging cells. 1239 53

The megakaryoblastic leukemia cell line MOLM-16 was established at relapse from the peripheral blood of a 77-year-old Japanese woman with minimally differentiated acute myeloid leukemia (AML-M0). Immunophenotyping of the fresh leukemic cells revealed a myeloid/NK precursor phenotype being positive for CD7, CD13, CD33, CD34, and CD56. In addition, megakaryocyte-associated antigens CD41 and CD61 were found to be positive. The established cell line designated MOLM-16 was proliferatively responsive to the treatment with various cytokines including EPO, GM-CSF, IL-3, PIXY-321, and TPO. MOLM-16 revealed characteristics of the megakaryocytic lineage in terms of immunophenotyping being positive for CD9, CD31, CD36, CD41, CD61, CD62P, CD63, CD110, CD151, thrombospondin, von Willebrand factor (vWf), and fibrinogen. Electron microscopic analysis showed positivity for ultrastructural platelet peroxidase in the nuclear envelope. The karyotype analysis of MOLM-16 revealed various numerical and structural abnormalities including t(6;8)(q21;q24.3), t(9;18)(q13;q21) and marker chromosomes. The extensive immunological, cytogenetic and functional characterization of MOLM-16 suggests that this cell line may represent a scientifically significant in vitro model which could facilitate the evaluation of megakaryocytic differentiation.
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PMID:Megakaryoblastic leukemia cell line MOLM-16 derived from minimally differentiated acute leukemia with myeloid/NK precursor phenotype. 1252 22

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

The two acute myelomonocytic leukemia sister cell lines MOLM-17 and MOLM-18 and the Epstein-Barr-virus positive non-malignant B-lymphoblastoid cell lines (B-LCLs) B422 and B423 were established from the bone marrow sample of a 60-year-old Japanese male in the advanced leukemic phase of refractory anemia with excess of blasts, a subtype of myelodysplastic syndromes (MDS). MOLM-17/-18 are proliferatively responsive to the growth factors present in the culture supernatant of the 5637 cell line. The B-LCLs are constitutively growth factor-independent. MOLM-17 and B422 were established at eight months after the initial diagnosis, while MOLM-18 and B423 were derived from a sample one month later. Immunophenotyping of the first leukemia sample revealed a mixed lineage leukemia immunophenotype with positivity for terminal deoxynucleotidyl transferase (TdT), CD13 and CD19; the second sample revealed solely myeloid characteristics with positivity for CD13, CD41 and CD61, whereas TdT was negative. MOLM-17/-18 showed immunomarker profiles typical of the myelomonocytic lineage. The karyotype analysis of MOLM-17/-18 revealed various non-random numerical and structural abnormalities including del(5)(q?), -7, der(11)add(11)(p11.2)add(11)(q23), add(17)(p11.2), add(18)(p11.2), -20, -22 as common aberrations. Treatment with tumor necrosis factor-alpha induced pronounced cellular differentiation of both cell lines into macrophage-like cells. The overall profile of MOLM-17/-18 based on their extensive immunological, cytogenetic and functional characterization suggests that these cell lines together with the paired B-LCLs B422 and B423 may represent scientifically significant in vitro models which could facilitate investigations into the pathobiology of MDS.
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PMID:Acute myeloid leukemia cell lines MOLM-17 and MOLM-18 derived from patient with advanced myelodysplastic syndromes. 1586 12

Valproic acid (VPA), a histone deacetylase inhibitor, causes differentiation in different cell lines and in a cell-specific manner; yet, its effect on megakaryocytic (MK) differentiation has not been studied. We evaluated whether VPA induces MK differentiation in a UT-7 cell line through histone acetylation in the GpIIIa gene region and activation of the ERK pathway. UT-7 cells, derived from megakaryoblastic leukemia, were treated with VPA at various concentrations, and the expression of differentiation markers as well as the gene expression profile was assessed. Flow cytometry, immunoblot analysis, and RT-PCR demonstrated that VPA induced the expression of the early MK markers GpIIIa (CD61) and GpIIb/IIIa (CD41) in a dose-dependent manner. The VPA-treated cells showed hyperacetylation of the histones H3 and H4; in particular, histone acetylation was found to have been associated with CD61 expression, in that the GpIIIa promoter showed H4 hyperacetylation, as demonstrated by the chromatin immunoprecipitation assay. Furthermore, activation of the ERK pathway was involved in VPA-mediated CD61/CD41 expression and in cell adhesion, as demonstrated by using the MEK/ERK inhibitor U0126. In conclusion, the capacity of VPA to commit UT-7 cells to MK differentiation is mediated by its inhibitory action on HDAC and the long-lived activation of ERK1/2.
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PMID:HDAC inhibition is associated to valproic acid induction of early megakaryocytic markers. 1673 51

Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bone-marrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.
Leukemia 2007 Feb
PMID:Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. 2700 46

The aim of this study was to investigate the clinical, pathological and biological features of acute megakaryoblastic leukemia in childhood. The morphology of cells was observed by means of bone marrow smear; the immunophenotype was detected by flow cytometry and immunohistochemistry assay. The results indicated that the fever, hemorrhage, hepatosplenomegaly and lymphadenopathy in this case were the primary presentations accompanying by leukocytosis, anemia and thrombocytopenia. An adequate marrow aspirate could not be obtained. At the time of diagnosis, the bone marrow had more than 30% megakaryoblasts in nucleated cells. Flow cytometric analysis revealed the dual expression of CD41 and CD61 by tumor cells in bone marrow. The histopathological examination of bone marrow demonstrated infiltration of large-sized CD42b(+) cells. According to all above mentioned results, this case was diagnosed as acute megakaryoblastic leukemia. In conclusion, childhood acute megakaryoblastic leukemia is a rare and easily misdiagnosed disease with poor prognosis. Flow cytometry analysis and immunohistochemistry assay of bone marrow can help in detecting this leukemia subtype and evaluating its prognosis.
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PMID:[Childhood acute megakaryoblastic leukemia]. 1760 59

Acute megakarioblastic leukemia (AMKL) is a rare myeloproliferative syndrome with a fulminant clinical course characterized by progressive pancytopenia, palior, weakness and severe haemorrhage. Two cases of AMKL are presented: a 18-year old male with pancytopenia and massive haemorrhage, lymphadenopathy, organomegaly and mediastinal tumour. The diagnosis of AMKL was established by cytological and immunocytochemical analyses of peripherial blood cells (blasts were GPIIIa and GPIb postitive), by histological analysis or the bone marrow and lymph node, and immunohistochemical analysis of lymph node. The second case had megakarioblastic transformation of HGL which was confirmed by cytomorphological and immunophenotypical analyses. In spite of therapy, the patients died soon after the first signs of the disease.
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PMID:[Acute megakarioblastic leukemia: de novo and transformation of chronic myeloid leukemia]. 1797 64

A 5-year-old male cynomolgus monkey (Macaca fascicularis) with a clinical history of bleeding tendency, severe anaemia, thrombocytopenia and elevated serum concentration of liver-related enzymes was examined post mortem. Ecchymotic haemorrhages were present on the left eyelid and forehead. The liver, kidney and spleen were markedly enlarged and the kidneys had capsular petechiae. Microscopically, numerous atypical cells resembling myeloid cells were observed in the bone marrow, and myelofibrosis was present. Atypical cells were also present in the blood vessels of the liver, kidney, spleen, lymph nodes, lung, heart, bladder, adrenal gland and brain. Some neoplastic cells had oval or pleomorphic macronuclei and others were multinucleated. Immunohistochemically, the majority of the neoplastic cells had granular cytoplasmic expression of the megakaryocyte-associated antigens Von Willebrand Factor and CD61-IIIa, but were negative for myeloperoxidase. A diagnosis of acute megakaryocytic leukaemia (AMKL)-like disease was made. This would appear to be the first report of AMKL-like disease in non-human primates. This monkey was infected with simian retrovirus type D and it is possible that this viral infection was associated with the development of neoplasia.
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PMID:Acute megakaryocytic leukaemia (AMKL)-like disease in a cynomolgus monkey (Macaca fascicularis). 1915 98

Natural killer (NK) cell neoplasms are a group of rare but highly malignant tumors. We report here one case of NK cell leukemia. A 54-yr-old woman presented with a 2-month history of progressive left neck mass. Based on the positive result of tissue PCR for Mycobacterium tuberculosis, she was at first diagnosed with tuberculous lymphadenopathy. After two weeks, she developed generalized lymphadenopathy, hepatosplenomegaly, fever and anemia. Subsequent evaluation was performed including bone marrow aspiration and biopsy. Peripheral blood smear showed leukoerythroblastic features with 31% blasts. Bone marrow was packed with agranular blastoid cells, which were periodic acid-Schiff (PAS) positive and myeloperoxidase (MPO) negative. Immunophenotyping showed that these cells were positive for CD45 and HLA-DR, whereas negative for CD3, CD5, CD7, CD10, CD13, CD14, CD19, CD20, CD22, CD33, CD34, and CD61. Because of the absence of the markers of T-cell, B-cell, and myeloid lineage-specific antigens, we added CD16/56 for the immunophenotyping and the blasts were positive (94%). The tumor cells of biopsied lymph node were only positive for CD56, consistent with NK cell lymphoma. Epstein-Barr virus (EBV) was not detected by RNA in situ hybridization. Culture for M. tuberculosis was negative. Thus this patient was diagnosed with blastic NK cell lymphoma/leukemia involving bone marrow and lymph node.
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PMID:A case of natural killer cell leukemia misdiagnosed as tuberculous lymphadenopathy. 1957 15


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