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

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of hematopoiesis entailing hyperproliferative and ineffective hematopoiesis resulting in refractory cytopenia(s), and increased risk of transformation into acute myeloblastic leukemia (AML). The widely used classification defined by the French-American-British group (FAB) recognizes 5 cytological subtypes of different prognosis, based essentially on the presence and the frequency of marrow blasts. The percentage of marrow blasts does not exceed 30%, hence, direct investigations of biological and biochemical events of MDS blast cells have been hampered. The CD34 antigen is currently unique in its narrow specificity of expression on human lymphohematopoietic progenitor cells. This cell membrane phosphoglycoprotein has been used for immunologic blast cell purification, notwithstanding the frequency of marrow blasts, and has provided a set of tools for investigations of MDS i.e. a direct comparison of the nature of blast cells in each of the MDS subtypes, using immunologic, biologic, biochemical and molecular biological methodology. A combination of serum-free medium and a purification method for blast cells provided evidence that the progenitor cell growth abnormalities in these disorders involve a defect in the capacity of progenitor cells to respond to stimulation with growth factor(s), and has presented direct evidence for the manner in which myelodysplastic CD34+ cells are impaired.
Leuk Lymphoma 1994 Jun
PMID:Impaired proliferation and differentiation of myelodysplastic CD34+ cells. 752 20

Immunological analysis of bone marrow cells in myelodysplasia using immunofluorescence did not allow accurate morphological identification of blast cells. However, improvement of the immunoperoxidase technique allows one to realize the diagnostic potential of immunocytochemistry. CD34 immunotyping of blasts in normal human bone marrow showed 0.8 +/- 0.4% CD34 positive blasts and these cells had the morphology of type 1 blasts. The increase of bone marrow blasts in RAEB patients is related to CD34 negative type II and III blasts. A clone of undifferentiated CD34 positive blasts is characteristic of RAEB-T and acute myeloid leukaemia evolving from myelodysplasia. The detection of CD34 positive bone marrow blasts allows a better discrimination between RAEB and RAEB-T.
Leuk Lymphoma 1994 Sep
PMID:CD34 immunophenotyping of blasts in myelodysplasia. 753 58

The major clinical experience with fludarabine has been obtained in patients with chronic lymphocytic leukemia (CLL). In the initial studies in previously treated patients with CLL, the complete and partial response rate (CR + PR) was over 50%, and in previously untreated patients with CLL, a CR + PR rate of 75-80% was noted with or without the addition of prednisone. Subsequent clinical trials have also demonstrated major activity with fludarabine in Waldenstrom's macroglobulinemia. Fludarabine was noted to be an active agent in indolent lymphoma in phase I/II studies. Approximately 60% of patients with follicular lymphoma respond to fludarabine when it is administered as a single agent. Many of these remissions are complete remissions despite patients having received extensive prior therapy. Combination programs are being developed for application in CLL and indolent lymphoma. Because of the activity of fludarabine in inhibiting DNA repair, it has been combined with cisplatinum and cytosine arabinoside and plans are in place to explore the radiation sensitizing effect of fludarabine in clinical trials. A combination of fludarabine plus ara-C is now being used in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) and a combination of fludarabine, ara-C, and G-CSF (FLAG) has been combined with idarubicin for the management of these conditions. Many of these activities of fludarabine are associated with its interaction with many enzymes which are important in DNA and RNA metabolism and in DNA repair. It is anticipated that these actions will be explored in a wider range of studies subsequently.
Leuk Lymphoma 1994
PMID:The expanding role of fludarabine in hematologic malignancies. 753 76

Peripheral blood stem cells (PBSC) were collected from 24 patients who were treated with high dose etoposide. Studied patients included one with acute lymphoblastic leukemia, 4 with acute myeloid leukemia (AML), 1 with myelodysplastic syndrome, 13 with lymphoma, 1 with malignant histiocytosis, 2 with myeloma, and 4 with testicular tumor. Etoposide was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant human granulocyte-colony stimulating factor from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all patients, the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the patients (73%). All leukemia patients treated along with our protocols have remained in complete remission, but one patient with AML relapsed within 1 month after the treatment. Ten lymphoma patients were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one patient. Two patients with myeloma were classified to be NC. Three of the 4 patients with testicular tumor were PR, and the other one was NC. Eleven patients subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.
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PMID:[Peripheral blood stem cell collection with high dose etoposide]. 754 Feb 21

A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph1)-positive ALL cells was produced. The reactivity of a monoclonal antibody, KOR-SA3544 (IgG2a) was evaluated on normal hemopoietic cells, 68 leukemic cell lines and freshly obtained cells from 190 patients with leukemia and lymphoma. In cultured cells, KOR-SA3544 reacted with Ph1-positive ALL cell lines (5/5) and leukemic cell lines with 11q23 translocation (3/11). In lymphoid cells, KOR-SA3544 was reactive with all of Ph1-positive ALL (26/26), a part of common ALL (5/38) and one case of early B precursor leukemia with 11q23 translocation, but not with peripheral lymphocytes. Normal mature granulocytes were also strongly stained. In myeloid leukemias, KOR-SA3544 was positive (16/56) only in patients with acute myeloid leukemia with FAB-M2 and overt leukemia following myelodysplastic syndrome, but neither with other types of myeloid leukemias nor with blast crisis in chronic myelogenous leukemia. KOR-SA3544 recognized a 90 KDa protein on the membrane of a leukemic cell line, KOPN-57bi. In normal bone marrow, CD19+/KOR-SA3544+ cells were not identified, while Ph1-positive ALL cells were strongly positive for both antibodies. KOR-SA3544 is useful not only for making the diagnosis of Ph1-positive ALL but for detection of the minimal residual disease during remission.
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PMID:A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity. 754 76

Acquired interstitial deletions of the long arm of chromosome 5, are seen in anomalies of the myeloid cells. The refractory anemia (RA) or 5q- syndrome, in which the erythroid and megakaryocytic lineages are predominantly affected, is a relatively indolent clinical entity distinguishable, from the constellation of preneoplastic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) with trilineage involvement. Recent molecular evidence suggests that the critical region of 5q deletion in MDS/AML resides in the D5S89 locus, which is proximal (centromeric) to the minimal region of loss in the 5q- syndrome RA. The invariable loss of the D5S89 locus in MDS/AML qualifies it for the MDS/AML tumor suppressor locus. The telomeric 5q31 gene governs erythroid and megakaryocytic differentiation and can be termed the RA locus. Isolation and characterization of these genes will lead to an understanding of molecular mechanisms underlying normal hematopoiesis and leukemic transformation.
Leuk Lymphoma 1995 May
PMID:Molecular analysis of the 5q- chromosome. 754 26

Recent clinical studies suggested that interleukin-2 (IL-2) has therapeutic potential for some hematologic malignancies, but the therapeutic role of IL-2 for myelodysplastic syndrome (MDS) is still unclear. MDS is a clonal malignant disorder which often involves a variety of immunologic abnormalities. Examination of the effects of IL-2 on MDS in vitro yielded the following results: (1) IL-2 did not induce the proliferation of blasts in most MDS cases. (2) The cytotoxicity of IL-2-induced lymphokine-activated killer (LAK) cells for cell lines and MDS blasts was reduced in the high-risk MDS group (refractory anemia with excess blasts (RAEB), RAEB in transformation and MDS transformed to acute leukemia), but it was still preserved in the low-risk MDS group (refractory anemia (RA) and RA with ringed sideroblasts). However, considerable variation in LAK cell cytotoxicity was noted in each group. (3) The reduced LAK cell cytotoxicity observed in MDS was explained, at least in part, by the presence of a reduced of number of natural killer (NK) cells amongst the LAK cells. (4) MDS patients who have a high blood soluble IL-2 receptor (sIL-2R) level often had defects in NK and CD8+ T cells. These in vitro findings suggest that the response to IL-2 is heterogeneous in MDS patients, and those who have a low-risk MDS subtype and/or a low blood sIL-2R level, may be prone to respond to IL-2 therapy. Clinical trials are mandatory in order to elucidate the efficacy of IL-2 therapy in the treatment of MDS.
Leuk Lymphoma 1995 May
PMID:Interleukin-2 therapy for myelodysplastic syndrome: does it work? 754 31

Inactivation of the deleted in colorectal carcinoma (DCC) tumor suppressor gene has been reported not only in colorectal carcinoma but also in other human malignancies. In order to evaluate the role of the DCC gene in leukemogenesis, we examined DCC expression using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Expression of the DCC gene was reduced or absent in 10 of 39 (26%) patients with acute myelogenous leukemia (AML), three of 14 (29%) patients with acute lymphocytic leukemia (ALL), seven of 33 (21%) patients with chronic myelogenous leukemia (CML), three of 39 (8%) patients with myelodysplastic syndromes (MDS), and five of nine (56%) patients with overt leukemia progressed from MDS. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.
Leuk Lymphoma 1994 Dec
PMID:Expression of the DCC gene in human hematological malignancies. 769 19

Myelodysplastic syndromes (MDS) are increasingly recognized as a cause of bone marrow failure, and are at least as frequent as acute myeloid leukemias. While the overall incidence is about 2-4/100,000/year, incidence figures rise steeply with age. Incidence rates of 20-30/100,000/year in persons over 70 demonstrate that MDS are among the most common hematological neoplasias in this age group. However, due to difficulties of diagnosis and classification, patient registration in population-based registers is far from complete. As a prerequisite for truly representative statistics, future revisions of disease classification systems must incorporate MDS as a separate group of disorders. The difficulties in conducting epidemiological studies also impede the identification of risk factors for the development of MDS. Current knowledge of occupational risk factors is also reviewed here. More rapid progress in our understanding of MDS may come from recent advances in methodology that have begun to shed some light on the cytogenetic and molecular aspects of leukemogenesis in general, and MDS in particular. Non-random chromosomal changes can be found in about 50% of cases at diagnosis, but they are probably late events in the evolution of MDS, reflecting the progressive genomic instability of the premalignant clone. Proto-oncogene mutations have also been suggested to be relevant to the pathogenesis of MDS, but longitudinal studies of point mutations of the N-ras proto-oncogene revealed that such events, although often associated with rapid deterioration and transformation to AML, also appear to be late events during the course of disease. Therefore, it remains a major challenge to identify those lesions that initiate the multistep development of preleukemia. As the incidence of MDS correlates strongly with age, it is reasonable to presume that age-dependent changes of the hematopoietic system may play a role in the initiation of MDS. Aging is probably associated with a compromised marrow reserve through reduction in the size of the stem cell pool. Through increased proliferative activity, the remaining stem cells may be particularly vulnerable to mutagenic insults. Immunological attack on stem cells, mitochondrial DNA mutations, and the regulatory influence of the hematopoietic microenvironment must also be considered as possibly contributing to the early stages of MDS.
Leuk Lymphoma 1995 Jan
PMID:Epidemiological and etiological aspects of myelodysplastic syndromes. 771 33

Trilineage myelodysplasia (TMDS) in de novo acute myeloid leukemia (AML) at initial diagnosis and during remission has not been well recognized yet. In this review we describe the characteristics of de novo AML with TMDS (AML/TMDS) and with myelodysplastic remission marrow (AML/MRM) in view of the in vivo and in vitro disease progression. AML/TMDS was found in ten (10.4%) of 96 patients with de novo AML at initial diagnosis and AML/MRM were also observed in three (5.0%) out of 60 cases in remission after chemotherapy in our hospital between 1984 and 1992. Abnormal karyotypes were seen in six of nine AML/TMDS patients and all of the three AML/MRM. Karyotypic changes occurred in two of AML/TMDS and two of AML/MRM during their clinical course. Using the long term bone marrow culture (LTBMC) system that allowed abnormal clones to survive preferentially to the clone of normal karyotype, latent clones were detected in three patients with AML/TMDS and three of AML/MRM as in the cases of myelodysplastic syndrome (MDS) and AML transformed from MDS (MDS/AML) but not in the typical AML without myelodysplastic changes. Four of these cases exhibited the same karyotypes as seen during the clinical course. Primary abnormal karyotypes prior to clonal evolution were also observed in two of the AML/MRM. Taken together, both AML/TMDS and AML/MRM are similar to MDS/AML with respect to their myelodysplastic background and potential for disease progression and may have progressed to AML from the preceding disease status more rapidly than MDS/AML.
Leuk Lymphoma 1995 Jan
PMID:De-novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) and myelodysplastic remission marrow (AML/MRM). 771 34


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