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)

PMN elastase is a useful additional parameter in the differential diagnosis of the leukaemias. In all patients with myelocytic leukaemias there were elevated levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI), while in the lymphatic leukaemias complexed elastase levels were decreased. The highest values were found in the peripheral blood plasma and bone marrow plasma of patients with CML. Despite high E-alpha 1PI concentrations there were no signs of bleeding or consumption of plasmatic coagulation factors. In AML a wide range of E-alpha 1PI levels was observed, extending from slightly elevated to four hundred-fold increased. In myeloblastic leukaemias without maturation (FAB M 1) the concentrations of complexed elastase remained below 150 ng/ml. In myeloblastic leukaemias with maturation (FAB M2) the E-alpha 1PI values ranged between 214 ng/ml and 850 ng/ml (means = 402 +/- 69), and in myelo-monoblastic leukaemias (FAB M4) between 450 ng/ml and 720 ng/ml (means = 663 +/- 72). The only case of promyelocytic leukaemia (FAB M 3) exhibited an extremely high value of 4,550 ng/ml, while a monocytic leukaemia (FAB M5) showed an extremely low value of 5 ng/ml. During cytostatic therapy there was a rapid decrease in levels of complexed elastase, with E-alpha 1PI values returning to normal in remission. In recidivating cases there was an increase of E-alpha 1PI levels in AML and a decrease in ALL. There was a correlation between the E-alpha 1PI concentrations in peripheral plasma and leukaemic bone marrow infiltration, so providing a good basis for monitoring remission from leukaemia and indicating relapse. It was also interesting to observe an extremely low E-alpha 1PI level (5 ng/ml) in patients with myelodysplasia. Under Decortin/Plenastril therapy the concentration rose to 50 ng/ml. An E-alpha 1PI level of 10 ng per ml was observed in one case of Ranitidine agranulocytosis. Under corticoid therapy the value returned to normal within eight days.
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PMID:The importance of granulocyte elastase in haematological diagnosis. 316 79

10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily.
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PMID:1 alpha(OH)D3 (ETALPHA) treatment and receptor studies in 16 patients with chronic and myeloproliferative disorders. 347 70

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) was administered p.o. to 199 patients with acute leukemia, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). Of 76 patients with AML, 11 achieved complete remission (CR) and 7 achieved partial remission (PR). Of 8 patients with ALL, 2 achieved CR and 1 achieved PR. Of 3 patients with blast crisis of MPD, 1 achieved CR. CR was reached with PL-AC at 100-900 mg/day after 5-98 (median 26) days. Of 50 patients with MDS, 2 achieved CR, 2 showed good response and 7 partial response. Response was reached with 100-400 mg/day after 13-122 (median 32) days. Improvement of polycythemia vera was observed in 6 of 13 patients, and reduction of thrombocytosis was observed in 20 of 23 patients with essential thrombocythemia and myelofibrosis. Of 18 patients with CML, 1 achieved CR. Major side effects were GI toxicities and myelosuppression. In spite of the disadvantages of the oral form of the drug, such as unpredictable absorption, PL-AC may be useful in the treatment of acute leukemia, especially that of the aged, a condition for which intensive chemotherapy is not always indicated, and MDS, which do not necessarily require admission to a hospital.
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PMID:[A phase II study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) in patients with acute leukemia and myelodysplastic syndromes. Cooperative Study Group for PL-AC]. 361 59

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.
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PMID:Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine. 689 90

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.
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PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and with leukemia following other hematopoietic proliferative diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even within a specific clinical phenotype. Interestingly some of the (3;21) breakpoints involve the AML1 gene previously found rearranged in the t(8;21) associated with acute myelogenous leukemia. AML1 is related to the Drosophila gene runt and is the human counterpart of the gene for the alpha subunit of the nuclear polyoma enhancer binding protein (PEBP2) also known as the core binding factor (CBF). In the t(3;21) AML1 was found rearranged with EAP, a gene on chromosome 3 encoding a small ribosomal protein, as well as with EV11, another gene on chromosome 3. Here we report our study of six cases of t(3;21). By using fluorescence in situ hybridization (FISH) analysis and AML1 probes we could conclude that at least in two CML-BC cases the breakpoint occurred in the AML1 intron that is disrupted by the t(8;21). An AML1/EAP fusion transcript, different from the one described in a therapy-related myelodysplasia, was detected in both CML-BC cases. This transcript is expected to result in a predicted protein containing the AML1 nuclear binding domain with an attached stretch of 17 amino acids unrelated to the EAP small ribosomal protein. In the other t(3;21) patients we could not detect an AML1/EAP transcript or an AML1/EV11 transcript. This result suggests heterogeneity of the t(3;21) at the molecular level. The AML1 chimeric transcripts identified so far, both in the t(3;21) and in the t(8;21), diverge from the normal transcripts either after exon 5 or exon 6. Here we show that in normal AML1 transcripts different splicing events are seen to occur after AML1 exon 5 as well as exon 6.
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PMID:AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular heterogeneity and usage of splicing sites frequently involved in the generation of normal AML1 transcripts. 753 26

Juvenile chronic myelogenous leukemia (JCML) is a heterogeneous disorder composed of Philadelphia chromosome-positive (Ph+) CML, which is similar to CML in adults, and Ph-negative (Ph-) CML, a childhood myelodysplasia resembling chronic myelomonocytic leukemia in adults. These two disorders are not always readily separable by leukocyte alkaline phosphatase (LAP) scoring and by karyotyping, yet they have different courses and outcomes. We compared the results of breakpoint cluster region (bcr) gene rearrangement analysis with LAP score and karyotype in these patients. In addition, analysis for immunoglobulin and T-cell receptor gene rearrangement was done to investigate the possibility of mixed myeloid and lymphoid lineage, which has been shown to occur in childhood acute myelogenous leukemia and CML in blast crisis. Peripheral blood and bone marrow samples from six patients with JCML aged 5 to 19 yr were analyzed. One case was Ph+, and five were Ph- by karyotyping. Two samples showed LAP scores of 5 and 11 (one Ph+ and one Ph-); others were normal. All were digested with EcoRI, HindIII, and BamHI for immunoglobulin heavy and light chains and T-cell receptor beta-chain analysis and, in addition, with BglII for bcr analysis. Samples were hybridized with probes to JH, JK, CT beta, and bcr (Oncor). A bcr rearrangement was shown in the Ph+ sample; all others, including one with a very low LAP score, were negative. No JH, JK, or CT beta rearrangements were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breakpoint cluster region, immunoglobulin, and T-cell receptor gene rearrangement analysis in juvenile chronic myelogenous leukemia. 756 36

There is compelling evidence that leukemia arises via a multistep process. Molecular analysis of human leukemias, which are typically clonal, commonly shows multiple genetic lesions in a single leukemia including chromosomal translocations, gene amplification, and point mutations, and in several cases the mutational activation of an oncogene and the loss of a tumor suppressor gene have been found in the same leukemic cell. Accumulative evidences suggest that a number of oncogenes and tumor suppressor genes are involved in the hematopoietic tumorigenesis. These mutations can be utilized for molecular diagnosis of human hematopoietic tumors. Among them, detection of chimeric gene generated by chromosomal translocation is especially useful for molecular diagnosis. The t(3;21) (q26;q22) translocation is found usually in blastic crisis of CML and leukemias developed from MDS or hematopoietic proliferative diseases, but never in de novo acute myelocytic leukemia. This raises the possibility that the molecular event underlying the t(3;21) translocation has a critical role in progression from a preleukemic state to a leukemic state. The generation of AML1/EVI-1 chimeric gene has been demonstrated to be consistent in t(3;21)-carrying leukemias. Although target genes remain to be elucidated for both AML1 and EVI-1 as transcription factors, the AML1/EVI-1 fusion protein could work on different set of genes critical to the process of proliferation and differentiation of hematopoietic cells.
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PMID:[Diagnosis of hematological disorders by mutational analysis of oncogenes]. 760 95

The aim of the present study was to evaluate the significance of immunomorphometric assessment of megakaryocyte size and number in normal and pathologic human bone marrow. Thus, we compared morphometric characteristics of megakaryocytes in 56 bone marrow trephine biopsies stained by immunohistochemical and conventional techniques. Morphometric results showed that precise megakaryocyte size in normal and pathologic samples can be calculated even by using conventional staining technique, but only employing specific stereological corrections. Immunomorphometric evaluation revealed populations of "small" megakaryocytes (< 14 microns), "morphologically unrecognized" by conventional staining technique (promegakaryoblasts in normal and stimulated as well as micromegakaryocytes in pathologic bone marrow). In patients with normal and stimulated megakaryocytopoises percentage of "small" megakaryocytes was generally low (10.6% and 14%, respect.); so, megakaryocyte number was similar in immunohistochemically and conventionally stained sections. In contrast, percentages of "small" megakaryocytes were significantly higher in patients with stem cell disorders (namely, myelodisplastic syndrome and chronic granulocytic leukaemia), as compared to controls (35.3% in MDS; 22.9% in CML and 10.6% in controls). In those patients megakaryocyte numbers were more sensitively detected by immunohistochemistry than by conventional staining.
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PMID:[Importance of immunomorphometric evaluation of the size and number of megakaryocytes in normal and pathologic bone marrow]. 771 37

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.
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PMID:Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia. 772 69


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