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)

We studied granulocyte-macrophage (GM) colony formation in chronic myelomonocytic leukemia (CMML, 6 cases), as compared with that in myelodysplastic syndromes (MDS, 6 cases) and myeloproliferative disorders (MPD, 12 cases). GM colony formation of bone marrow cells by colony-stimulating factor (CSF) was normal in CMML and MPD patients, but was decreased in MDS patients. Circulating granulocyte-macrophage progenitors (CFU-GM) were detected in CMML and MPD patients, but not in MDS patients. GM colony formation without CSF was observed in CMML patients, but not in MDS or MPD patients. These endogenous colonies decreased markedly after adherent cell (AdC) depletion, but AdC did not form endogenous colonies in sufficient numbers to explain their marked decrease after AdC depletion. In CMML patients, the numbers of circulating CFU-GM and endogenous colonies correlated with leukocyte and monocyte counts, respectively. The cellular composition of GM colonies was normal in MDS and MPD patients, whereas granulocytic colonies predominated in all CMML patients but one. The CSF-producing capacity of peripheral blood cells was also studied and was found to be increased in CMML patients. This capacity was markedly decreased by AdC depletion; and AdC could produce CSF only in CMML patients. CSF produced by CMML patients supported granulocytic colonies to a greater extent than CSF produced by MDS or MPD patients. These results suggest that enhanced granulopoiesis in CMML patients is closely associated with the possible hyperproduction of granulocytic CSF by their adherent monocytes.
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PMID:Characteristics of granulocyte-macrophage colony formation in chronic myelomonocytic leukemia: a comparative study with other myelodysplastic and myeloproliferative disorders. 211 95

This thesis is a survey of nine previously published articles on MPO deficient PMN. The incidences in leukaemia and allied disorders of the presence of this abnormal subpopulation of mature neutrophils and the relationship to clinical course in AML, susceptibility to infections in AML, FAB classification in AML and MDS, cytogenetically defined aberrations in MDS and morphometrical characteristics were investigated. The aims of the studies were to examine the diagnostic as well as the prognostic value of the parameter, to examine the usefulness of the parameter as an predictive indicator of CR and relapse in AML and to examine the concept that MPO deficient PMN may originate from leukaemic precursors. MPO deficient PMN were found to occur in a minor number (less than 4% of the total number of PMN) in normal humans and the incidences of an abnormal number (greater than 4%) were found to be about 40% in AML (I, II, III, IV, VIII), 60% in CML (I, VII), 30% in MPD other than CML (VII) and 30% in MDS (V). The highest incidences in AML were found in the FAB subtypes possessing the most myeloid differentiation potential i.e. FAB M2 and FAB M4 (IV). In ALL, CLL, HCL, Hodgkin's disease, anaemia not related to leukaemia and leukaemoid reactions the incidences all were 0% (I, unpublished data). The abnormal MPO deficient PMN subpopulation, if present, disappeared when CR was achieved and reappeared when relapse eventually was developed (II, VIII). In both situations serial determinations showed that the change occurred before the usual routine blood examinations predicted CR and relapse; several days and several months prior, respectively (VIII). The probability of obtaining CR was lower in the AML patients with the abnormal subpopulation and the risk of developing relapse higher than in AML patients without the anomaly (II, VIII). These differences were not statistically significant, however. AML patients, showing an increased number of MPO deficient PMN, revealed a statistically significant increased susceptibility to infections (P less than 0.01) during the preremission phase accounting for 18% to 67% of the total number of infections in this period (III). This increase was positively correlated to the extent of the anomaly (P less than 0.002). The spontaneous occurrence of a subpopulation of MPO deficient PMN in MDS went together with a simultaneous progression in cytogenetically determined clonal chromosomal aberrations and were related to progression in FAB subtype as well (VI). Morphometrically MPO deficient PMN were characterized by a decreased total cell size and an increased nucleus size of the projected images (IX).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myeloperoxidase deficient polymorphonuclear leucocytes in leukaemia and allied disorders. 285 15

Several large cohorts of patients treated with alkylating agents served as a means to review the clinical and pathologic features of 55 cases of myelopathic disorders that resulted. The incidence was 1.8% overall and consisted of five patients (9.9%) who developed bone marrow hypoplasia or aplasia, 15 (27.2%) who developed a myelodysplastic syndrome, and 35 cases of acute myeloid leukemia (62.9%). The median time to recognition of MPD was 14 months, following cessation of chemotherapy. The distribution of the treatment-related MDS cases was different than "de novo" MDS with a high percentage of RAEB-T, and with the treatment related AMLs, there were a higher percentage of patients with FAB M6 (erythroleukemia), and no cases of FAB M3 (hypergranular promyelocytic). The median survival of all patients was very brief.
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PMID:Acute myeloid leukemia and other myelopathic disorders following treatment with alkylating agents. 350 35

We have presented a working hypothesis showing the possible interrelations between proliferative, aproliferative and autoimmune disorders that may follow infection with lymphotropic herpesviruses. Aproliferative disorders in this context may also indicate immune or hematopoietic deficiency. Although this hypothesis can currently be best documented with the lymphotropic viruses (herpesviruses as well as similarly HTLV and HIV), the model may apply as well--with certain variations--to other viral infections such as with hepatitis virus B or C with acute or chronic infectious diseases, post-infectious arthritis, aplastic anemia, and other autoimmune liver diseases, as well as neoplastic diseases (hepatocellular carcinoma, chronic lymphocytic leukemia). The working hypothesis as depicted in Figure 2 permits a preview of which combinations of symptoms may occur in an individual disease independent of its initial classification and what clinical testing should be done respectively, and it also permits certain prognostic considerations. The above-mentioned transitions or combinations of various disease patterns have been repeatedly described in the medical literature (to refer to only a few examples: APL and MPD, HD and MDS, SLE and aplastic anemia, SLE and Kikuchi's disease; 23, 80-83). Finally the hypothesis can ideally serve as the basis for future planning of clinical research.
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PMID:A unifying concept of viral immunopathogenesis of proliferative and aproliferative diseases (working hypothesis). 789 76

The cytogenetic findings of therapy-related myeloid leukemia (t-ML) in three children are presented. These included one male patient with acute lymphoblastic leukemia (ALL) who underwent bone marrow transplantation and developed therapy-related myeloproliferative disease (t-MPD) in the female-donor hematopoietic cells 2.5 years after receiving radiation and epipodophyllotoxin therapy for ALL testicular relapse. Bone marrow leukemic cell karyotype revealed 46,XX,add (11)(p15) and a normal female karyotype in the peripheral blood lymphocytes. The other two children, one with ALL and one with ganglioneuroblastoma, developed fatal t-MPD and therapy-related acute myeloblastic leukemia (t-AML) preceded by myelodysplastic syndrome (t-MDS), respectively, 5 years after diagnosis, following administration of alkylating agents and irradiation. Monosomy 7 was present in both, and was combined with inv(3)(q21q26) in the second patient. Our review of the cytogenetic findings in 91 previously reported pediatric patients with t-ML suggested that the involvement of 11p15 and 3q21-->23, 3q24-q26 with or without a combination of translocation 11q23 and -7/7q-, respectively, are nonrandom aberrations of t-ML in children. Comparison of the chromosomal changes in t-ML between the pediatric and an adult series revealed some differences which may result from differences in treatment modalities and which, in addition, may indicate a possible role of genetic and/or age-dependent factors in the pathogenesis of therapy-related leukemogenesis in children.
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PMID:Involvement of 11p15 and 3q21q26 in therapy-related myeloid leukemia (t-ML) in children. Case reports and review of the literature. 803 58

One of the first known effects of the endogenous peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) is to inhibit entry into DNA synthesis of pluripotent haematopoietic stem cells (CFU-S) in mice. A specific anti-AcSDKP polyclonal antibody allows the level of the tetrapeptide by to be determined by enzyme immunoassay with good sensitivity and specificity. We present results demonstrating the presence of AcSDKP in humans: serum levels of 34 healthy controls were found to be between 0.7 and 2.5 pm/ml, regardless of age and sex. High levels were found in 44% of asymptomatic controls but only in 8% of AIDS patients out of a total of 37 patients with HIV. Subsequently, studies of serum levels were performed before treatment in 121 subjects with disorders of the nonlymphoid and the lymphoid lineages. Our results did not demonstrate any decrease in serum levels, however a moderate or marked increase was noted in one-third of the subjects, which was greater in disorders of the non-lymphoid lineages (48% of 72 patients) than the lymphoid lineage (21% of 50 patients). The most significant differences were observed between controls versus patients with myeloproliferative disorders (MPD, 24 patients: p < 0.001), controls versus patients with acute myelogenous leukaemia (AML, 15 patients: p < 0.02), as well as patients with AML versus patients with primary myelodysplastic syndromes (PMDS, 10 patients: p < 0.05). The pathophysiology of these abnormalities is discussed.
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PMID:Serum levels of a negative regulator of cell proliferation (AcSDKP) are increased in certain human haemopathies. 850 76

The human erythropoietin receptor (EpoR) gene has been cloned and characterized. Very few EpoR genetic abnormalities have been reported so far. Polycythemia vera (PV) is characterized by low/normal serum erythropoietin (Epo) levels with proposed Epo hypersensitivity. Myelodysplastic syndromes (MDS) are characterized by refractory anemia with variable serum Epo levels. Several reports have suggested EpoR abnormalities in both types of stem cell disorders. We analyzed DNA obtained from peripheral blood mononuclear cells of seven healthy controls, 20 patients with myeloproliferative disorders (MPD, 11 patients with PV, five agnogenic myeloid metaplasia with myelofibrosis, four essential thrombocytosis) and eight patients with refractory anemia with ringed sideroblasts (RARS), an MDS variant. The DNA was digested with four restriction enzymes (BamHI, Bgl II, Sacl and HindIII), followed by Southern blot, using a 32P radiolabeled probe, containing 1.5 kb of the human EpoR cDNA. All 20 MPD patients and seven out of the eight MDS patients demonstrated a restriction pattern which was identical to the seven normal controls, as well as to the erythroid cell line K562, and also consistent with the expected restriction map, for all four enzymes tested. One RARS patient had a normal pattern with three enzymes but a different one with HindIII. The HindIII 12 kb large band was replaced by a faint 12 kb band and a new (about 9 kb) band appeared. The EpoR restriction map and the normal pattern obtained with the other three enzymes suggest that this patient has a 3 kb upstream deletion in one allelic EpoR gene. The same molecular pattern was detected in the patient's sister, who suffers from anemia with mild bone marrow (BM) dyserythropoiesis and plasmacytosis. Northern blot analysis showed that the patient's BM RNA carried normal EpoR message. This familial pattern may represent polymorphism. However, the patient's very high serum Epo level, her resistance to treatment with recombinant Epo, and the abnormally low growth rate of in vitro erythroid cultures, suggesting poor response to Epo in this MDS patient as well as the hematological abnormalities in her sister, support the speculation that the different EpoR gene might serve as a genetic predisposing marker and potentially could be involved (probably via post-transcriptional mechanisms and by an interaction with other factors or cytokines) in the pathogenesis. Our data suggest that the EpoR is intact in MPD and in most patients with RARS. One RARS patient had a familial different genetic structure, which could represent polymorphism. However, we can speculate also that it might be involved in the pathogenesis of the disease.
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PMID:Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes. 870 17

CD117 is a transmembrane protein receptor encoded by the c-kit proto-oncogene. The CD117 ligand is stem cell factor, an important hematopoietic regulator. CD117 is present on approximately 4% of normal bone marrow mononuclear cells and in acute myelogenous leukemia (AML) and chronic myelogenous leukemia in myeloid blast crisis, but rarely in acute lymphoblastic leukemia (ALL). Initially viewed as a primitive myeloid marker, CD117 has been identified in all FAB subtypes of AML and may predict poor outcome. CD34, a primitive stem cell marker, may also predict poor outcome. The aim of this study was to examine the relationship between CD117 and CD34 expression on leukemic blasts and to determine whether CD117 is related to lymphoid-associated antigen (LAA) expression in AML. Consecutive bone marrow samples were studied from cases of AML (30 cases), myelodysplastic syndromes (MDS) (4 cases), myeloproliferative disorders in blast crisis (MPD-BC) (6 cases), and ALL (5 cases). Cases were diagnosed according to FAB criteria and included M0 (3 cases), M1 (2 cases), M2 (13 cases), M3 (1 case), M4 (6 cases), M5 (3 cases), M6 (1 case), AML NOS (1 case), RAEB (3 cases), and RAEB-T (1 case). CD117 and CD34 were analyzed by multiparameter flow cytometry. Blasts in 10 de novo AML samples were CD117+/CD34+ in 4 cases, CD117+/CD34-in 3 cases, CD117-/CD34+ in 1 case, and CD117-/ CD34- in 2 cases. Blasts in 20 cases of relapsed AML were CD117+/ CD34+ in 13 cases, CD117+/CD34- in 6 cases, and CD117-/CD34+ in 1 case. Blasts in MDS were CD117+/CD34+ in 3 cases, CD117-/ CD34+ in 1 case. Blasts in MPD-BC were CD117+/CD34+ in 4 cases, CD117-/CD34+ in 2 cases. Blasts in ALL were CD117+/CD34+ in 1 case, CD117-/CD34+ in 1 case, CD117-/CD34- in 3 cases. Of 26 cases of CD117+ AML, CD4 was expressed in 15 (58%) cases, CD7 in 7 (27%) cases, and CD2 in 2 (8%) cases. CD117/CD34 expression did not correlate with FAB subtype of AML. CD117 is borne on most leukemic blasts of myeloid origin (in this study, 87% of AML, 80% of MPD-myeloid BC, and 75% of MDS) and does not exclude expression of LAA. Although CD117 is a receptor for stem cell factor, its expression does not appear to correlate with CD34 positivity.
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PMID:CD117/CD34 expression in leukemic blasts. 871 72

We examined the endonuclease activity capable of inducing internucleosomal DNA fragmentation in hematopoietic cells. Mg(2+)-dependent nuclease activity was high in hematopoietic progenitor cells and the activity decreased with myeloid or erythroid differentiation. This was the case in MDS as well as in normal hematopoiesis. In contrast, Ca2+/Mg(2+)-dependent nuclease activity varied widely in the samples from MDS and the possibility was indicated that the activity of Glycophorin A+ cells was related to the degree of anemia. We also investigated DNA strand breaks in bone marrow samples from 16 patients with MDS and 10 with other diseases by an in situ end labeling (ISEL) technique. The reactivity in ISEL tended to increase parallel to disease progression of MDS. The high ISEL-positivity was also observed in some samples from patients with MPD and other diseases. Though ISEL is a useful technique for quantification of apoptosis, our results suggested that MDS cells with ISEL positive staining are not necessarily in the process of apoptosis.
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PMID:[Apoptosis in MDS]. 877 68

Stored, fixed cell suspensions of bone marrows from 70 patients karyotyped over a three-year period for myelodysplastic syndrome (MDS) or related hematologic conditions were retrospectively studied in two series using centromeric probes for chromosomes 7 and 8. Series I consisted of patient samples with numerical and/or structural abnormalities of chromosomes 7 or 8, matched with chromosomally normal samples from about the same time period. Series II consisted of consecutive MDS patient samples as well as patient samples in which one or more cells had numerical or structural abnormalities of 7 and 8. In both series, probes for chromosomes 7 and 8 were applied in each case and at least 100 nuclei were scored for each probe for the distribution of one, two, or three signals. Twenty-seven cases had clonal abnormalities by routine cytogenetics (RC): 12 with monosomy 7; one with monosomy 8; five with trisomy 8; nine with clonal abnormalities other than 7 or 8 aneuploidy. Eleven cytogenetically normal cases gave abnormal interphase FISH (IF) results; one was subsequently confirmed by metaphase FISH analysis to have a clonal structural abnormality of chromosome 7; one case with a trisomy 8 clone, in remission by RC, showed 35% of cells by IF with three signals for chromosome 8; one case had heteromorphic chromosomes by FISH. Of eight remaining cases, five (four with -7 and one with +8 by IF) were among 22 cases of cytogenetically normal MDS. Three remaining cases (two with +8 and one with both +7 and +8 by IF) had AML or MPD. The high rate of possible undetected monosomy 7, among MDS cases in particular, suggests all MDS cases should be screened by IF.
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PMID:Fluorescence in situ hybridization to assess aneuploidy for chromosomes 7 and 8 in hematologic disorders. 1043 40


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