Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.
 ...
PMID:Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes. 916 61

A 40-year-old male with Ph-positive CML underwent PBSC autografting after initial treatment with hydroxyurea and interferon. Following autograft he remained in chronic phase with cytogenetic or molecular evidence of low levels of residual Ph-positive cells. However, additional cytogenetic abnormalities, including t(3;21) typically seen in therapy-related myelodysplastic syndrome (MDS) and AML and blast crisis of CML, developed as an independent cell line following the autograft. More than 4 years after the autograft, the patient remains in chronic phase with no evidence of accelerated phase or blast crisis of CML, but with a concurrent MDS. We report a case of CML who developed therapy-related MDS following PBSC autograft while still remaining in chronic phase.
 ...
PMID:t(3;21) following peripheral blood stem cell transplantation in chronic phase chronic myeloid leukaemia. 920 22

Idarubicin is an anthracycline agent available as both oral and intravenous formulations. The oral formulation has demonstrated efficacy in the treatment of advanced breast cancer, low-grade non-Hodgkin's lymphoma, myelodysplastic syndromes and as first-line induction therapy of acute myelogenous leukaemia where intravenous anthracycline treatment is precluded. It also has potential in ameliorating blast crisis of chronic myelogenous leukaemia and in multiple myeloma. The most frequent adverse effects associated with oral idarubicin are those commonly found with anthracyclines, namely myelosuppression, nausea and vomiting, diarrhoea and mucositis. There appears to be minimal significant cardiotoxicity with oral idarubicia. In summary; available data concerning oral idarubicin in haematological malignancies and advanced breast cancer are sufficiently encouraging to warrant further research. To maximise the use of oral idarubicin, future studies should define the optimal dose for elderly patients, its comparative efficacy with other available regimens and address quality-of-life and pharmacoeconomic issues associated with the substitution of oral for intravenous chemotherapy.
 ...
PMID:Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer. 923 41

We have identified three unbalanced translocations involving chromosomes 5 and 17, der(5)t(5;17), der(17)t(5;17), and dic(5;17), in the malignant cells from 17 patients with myeloid neoplasms. Six patients had a primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) de novo; ten patients had therapy-related MDS and/or AML (t-MDS/t-AML), and one patient had chronic myelogenous leukemia in myeloid blast phase. Two of the six patients with MDS or AML de novo had extensive exposure to industrial solvents, and one patient had Seckel syndrome. The primary diagnoses for the ten patients with t-MDS/t-AML were breast carcinoma and Hodgkin's disease in two patients each, and non-Hodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia, ovarian carcinoma, thyroid carcinoma, and rhabdomyosarcoma in one patient each. Four patients had received both prior chemotherapy and radiotherapy, four others received prior chemotherapy only, and the remaining two patients only prior radiotherapy. Fluorescence in situ hybridization of centromere-specific probes for chromosomes 5 and 17 revealed that a dicentric rearrangement was the most common (13/16 patients examined). The genetic consequences of these chromosomal rearrangements are partial monosomy for 5q and 17p. Two of six patients examined had point mutations in TP53, suggesting that loss of function of TP53 in addition to loss of a tumor suppressor gene on 5q may be involved in the pathogenesis of the malignant disease in some of these patients.
 ...
PMID:dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53. 936 36

A 49-year-old woman patient with atypical myelodysplastic syndrome (MDS) showing a der(3)t(3;12)(q21;p13), and der(12)t(3;12)(q21;p13)inv(3)(q21q26) as an acquired chromosomal abnormality in the bone marrow is described. The chromosomal breakpoints of the presented complex aberration with combination of the inv(3)(q21q26) and t(3;12)(q21;p13) were defined by fluorescence in situ hybridization (FISH) with yeast artificial chromosomes (YACs). The inv(3) is a relatively frequent chromosomal rearrangement in patients with myeloid malignancies and dysmegakaryopoiesis and t(3;12)(q26;p13) has also been reported as a recurrent abnormality in MDS and in blast crisis of chronic myelogenous leukemia (CML). Whereas the t(3;12), inv(3), and t(3;3) are associated with a very poor prognosis, our patient surprisingly had a mild clinical course.
 ...
PMID:A case of atypical myelodysplastic syndrome with micromegakaryocytes, normal platelet count, and t(3;12)(q21;p13) with inv(3)(q21q26). 936 37

We analyzed the expression of the Thy-1 antigen (CD90) in CD34+ acute leukemia using two-color flow cytometry. Leukemic cells were obtained from the bone marrow (BM) and/or the peripheral blood (PB) of 57 patients: 37 with acute myelogenous leukemia (AML) including nine with secondary AML following myelodysplastic syndrome (MDS/AML), and 20 with acute lymphoblastic leukemia (ALL) including three with chronic myelogenous leukemia in blast crisis (CML-BC) of the lymphoid type. Among these patients, one (3.6%) with de novo AML, two (22.2%) with MDS/AML, three (17.6%) with de novo ALL, and two (66.7%) with CML-BC coexpressed CD34 and Thy-1 (CD34+ Thy-1+) on more than 20% of the mononuclear cells within 'lymph' plus 'blast' window. Thy-1 was rarely expressed in de novo acute leukemia especially in AML. Interestingly, in 1 patient with CML-BC, the leukemic cells in BM were divided into two subpopulations (CD34+ Thy-1low and CD34+ Thy-1high), whereas most of the CD34+ leukemic cells in PB were Thy-1high. However, the mechanism for the mobilization of CD34+ Thy-1high leukemic cells into the PB is unknown.
 ...
PMID:Flow cytometric analysis of Thy-1 expression in CD34-positive acute leukemia. 940 Dec 77

We have used Southern blotting and fluorescence in situ hybridization (FISH) to define the breakpoints of a reciprocal translocation, t(10;12)(q24;p13), acquired as a secondary abnormality in a patient with Philadelphia chromosome positive chronic myeloid leukemia (CML) in transformation. A YAC clone that spanned the breakpoint at 12p13 was identified; this YAC included the CDKN1B gene but did not include ETV6. Neither ETV6 nor CDKN1B was rearranged, as determined by FISH and Southern blotting; however, a small deletion encompassing the translocated CDKN1B allele was detected. Analysis of two candidate genes at 10q24, HOX11 and NFKB2 suggested that they are not involved in this translocation. The preliminary mapping of breakpoints in this case demonstrated that they are different from an apparently identical translocation identified previously in a patient with myelodysplastic syndrome. The identification of the split YAC and small deletion should enable a more focused search for a gene or genes that may contribute to progression from chronic phase to blast crisis in CML.
 ...
PMID:Characterization of a t(10;12)(q24;p13) in a case of CML in transformation. 940 58

Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood, that is peculiarly characterized by the ability of bone marrow progenitors to spontaneously proliferate in vitro, giving rise to granulocyte-macrophage colonies. Although the genetic alteration/s leading to JMML development are still unclear, several lines of evidence indicate that the JMML initiating cell (JMML-IC) may belong to the pool of early stem-like hematopoietic progenitors. Increased EVI-1 gene expression has been detected in a number of myeloproliferative disorders including MDS, AML, blast crisis of CML, and more recently in the peripheral blood of some JMML patients. In order to investigate the nature of the cells expressing EVI-1 in JMML patients, we analyzed its expression in CFU-GM obtained from bone marrow and peripheral blood as well as from highly purified CD34+ progenitors. Normal CFU-GM obtained both from bone marrow mononuclear cells and from highly purified CD34+ cells were also analyzed. Overall, our results suggest that the EVI-1 gene may be normally expressed in early hematopoietic progenitor cells and that in JMML patients an expansion of the EVI-1 positive cell population can be revealed within the clonogenic progenitor pool.
 ...
PMID:EVI-1 gene expression in myeloid clonogenic cells from juvenile myelomonocytic leukemia (JMML). 944 18

RAS mutations can be detected in a variable number of patients with myeloproliferative disorders such as myelodysplastic syndromes and acute myeloid leukemia, but are rare events in chronic myelogenous leukemia in chronic phase. However, there is good evidence supporting the involvement of RAS signalling pathway in CML and this could be due to alterations in RAS activity regulatory proteins. The neurofibromatosis (NF1) gene down-regulates the RAS signal transduction pathway through the inhibitory function of its GAP-related domain (GRD) on RAS protein. The loss or alteration of neurofibromin (the NF1 protein) may produce a disfunction similar to point mutations in the RAS gene resulting in the permanent stimulation of the RAS signal transduction pathway. Mutations involving the GRD region of the NF1 gene (GRD-NF1) have been described in a variety of tumors such as colon carcinoma and astrocytoma. Germline mutations and deletions in the NF1 gene, as seen in neurofibromatosis type 1, are also associated with certain myeloid disorders. In the present work, we sought to identify mutations in the codons 12/13 and 61 of RAS gene and in the Lys-1423 codon of GRD-NF1, which are well known hot spots in these genes, in a group of 36 adults and ten children with chronic myelogenous leukemia in chronic phase and blast crisis. Using the PCR-SSCP and the allele-specific restriction assay (ASRA) techniques, we were not able to observe any RAS or NF1 detectable mutation. These findings suggest that RAS and GRD-NF1 mutations are not involved either in chronic phase or in the progression to blast crisis in chronic myelogenous leukemia in adults and children.
 ...
PMID:Mutational analysis of N-RAS and GAP-related domain of the neurofibromatosis type 1 gene in chronic myelogenous leukemia. 978 2

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.
 ...
PMID:Expression patterns of costimulatory molecules on cells derived from human hematological malignancies. 989 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>