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)

To find the best immunohistochemical marker for megakaryocytes in normal marrow, myelodysplastic syndrome (MDS), and chronic myeloproliferative disorders (CMPD), 57 marrow biopsy specimens were studied semiquantitatively with immunohistochemical methods using a panel of 7 antibodies. The staining intensity was graded 0 to 3 for scoring 100 consecutive megakaryocytes in each stained section. The final score for each stain was the sum of these 100 megakaryocytes individually multiplied by their corresponding grade. In normal marrow (11 cases), the average scores for antivon Willebrand factor (vWF) and Ulex europaeus agglutinin-1 (UEA-1) were 177.1 and 195.1, respectively. The scores for the other 5 markers, including anti-platelet-derived growth factor-BB, 2 anti-transforming growth factor-beta 3, anti-CD61, and anti-CD79a ranged from 96.1 to 124.1. In MDS (27 cases), the scores were 200.8 (vWF), 152.6 (UEA-1), and 28.7 to 98.5 (others). In CMPD (19 cases), the scores were 220.5 (vWF), 179.2 (UAE-1), and 64.8 to 101.2 (others). These results show that vWF and UEA-1 are good immunohistochemical markers for megakaryocytes in normal marrow, and vWF is the best marker in MDS and CMPD. For routine practice, vWF is the most reliable marker for identifying atypical megakaryocytes, especially in the cases of 5q-syndrome and agnogenic myeloid metaplasia.
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PMID:von Willebrand factor is the most reliable immunohistochemical marker for megakaryocytes of myelodysplastic syndrome and chronic myeloproliferative disorders. 1076 51

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) can stimulate megakaryopoiesis in vitro in some myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) patients. We assessed PEG-rHuMGDF combined with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 3 (IL-3), IL6, stem cell factor (SCF) or erythropoietin in 40 MDS, 33 AML and 16 normal bone marrow samples. CD61-positive cells in suspension cultures increased with PEG-rHuMGDF alone in 20/25 RA + RAS, 11/14 RAEB + RAEBt and 29/33 AML cases. Further increases when IL-3 and/or SCF were added to PEG-rHuMGDF occurred in 14/20 RA + RAS, 8/13 RAEB + RAEBt and 18/26 AML cases. CFU-Mk growth was poor overall, but could be enhanced by PEG-rHuMGDF combinations in some patients. Stimulation of megakaryopoiesis by PEG-rHuMGDF can be augmented by IL-3 and SCF in many MDS and AML patients.
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PMID:Megakaryopoiesis in vitro in myelodysplastic syndromes and acute myeloid leukaemia: effect of pegylated recombinant human megakaryocyte growth and development factor in combination with other growth factors. 1079 78

We have established a new hematopoietic cell line from a patient with myelodysplastic syndrome (MDS), which was refractory anemia with excess blasts (RAEB). This cell line, designated TER-3, depends on several cytokines for long-term survival and growth, and requires interleukin-3 (IL-3) for continuous growth. Cytochemical analysis revealed that TER-3 cells are weakly dianisidine positive and nonspecific esterase positive, but peroxidase negative. The surface marker profile shows that the TER-3 cells are strongly positive for myeloid, lymphoid, and megakaryocytic antigens such as CD15, CD19, and CD61, and negative for some common multilineage antigens such as CD13, CD33, and CD34. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in multipotent stem cells. Dianisidine- and nonspecific esterase-positive TER-3 cells increase with granulocyte-colony stimulating factor (G-CSF) rather than with IL-3. These results suggest that the cell line is useful for understanding the mechanism underlying G-CSF-associated hematopoietic cell differentiation and activation in the patient with MDS.
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PMID:New human myelodysplastic cell line, TER-3: G-CSF specific downregulation of Ca2+/calmodulin-dependent protein kinase IV. 1206 61

To evaluate a potential therapeutic role for megakaryocyte growth and development factor (MGDF) in myelodysplastic syndromes (MDS) we compared the in vitro response of normal and myelodysplastic megakaryopoiesis to MGDF on bone marrow mononuclear cells from nine MDS patients and four healthy donors in a short term liquid culture system. The cells were incubated with MGDF alone (1 ng/ml, 10 ng/ml and 100 ng/ml) and in combination with 20 ng/ml stem cell factor, 2 U/ml erythropoietin (EPO) and 100 ng/ml interleukin-3 (IL-3). Cytospins were prepared after 4 days and 10 days for CD61 APAAP staining. In addition, the ploidy of propidium iodide stained CD61 positive cells were detected by flow cytometry. The CD61+ cell number significantly increased (13-fold after 4 days, 56-fold after 10 days of culture) when MGDF (100 ng/ml) was added to the normal bone marrow (NBM) cultures (P=0.0003; P=0.0001). In the MDS cultures the absolute number of endomitotic cells as well as the percentage of polyploid cells remained significantly lower than in NBM after 10 days (P=0.0001). The effect of MGDF on polyploidization of MDS cells was significantly dose dependent (P=0.0051). We found no correlation between peripheral platelet count, cellularity of the bone marrow, number of bone marrow megakaryocytes or FAB-subtype and response to MGDF. Additional administration of IL-3 resulted in a left-shift of megakaryopoiesis in both groups. Even though the response of myelodysplastic megakaryocytic progenitors to MGDF shows inter-individual variations, it is significantly impaired overall. Our data suggest that higher doses of MGDF may be able to ameliorate thrombocytopenia in a subgroup of MDS patients.
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PMID:In vitro response of myelodysplastic megakaryocytopoiesis to megakaryocyte growth and development factor (MGDF). 1248 65

Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.
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PMID:[LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies]. 1254 Sep 99

Megakaryocytes (MKs) undergo successive rounds of endomitosis during differentiation, resulting in polyploidy (typically, 16-64N). Previous studies have demonstrated that this occurs through an interruption of normal cell cycle progression during anaphase. However, the molecular mechanism(s) controlling this unique process is undefined. In the present report, we examine the effect of an Src kinase inhibitor, SU6656, on thrombopoietin (TPO)-induced growth and differentiation. Remarkably, when SU6656 (2.5 microM) was added to a megakaryocytic cell line, UT-7/TPO, the cells ceased cell division but continued to accumulate DNA by endomitosis. During this interval, CD41 and CD61 expression on the cell surface increased. Similar effects on polyploidization and MK differentiation were seen with expanded primary MKs, bone marrow from 2 patients with myelodysplastic syndrome, and other cell lines with MK potential. Our data suggest that SU6656 might be useful as a differentiation-inducing agent for MKs and is an important tool for understanding the molecular basis of MK endomitosis.
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PMID:Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. 1567 65

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

Aplastic anemia (AA) is marrow failure due to an inadequate number of hematopoietic cells in the marrow. Prior reports have described a more aggressive clinical course in aplastic anemia with monosomy 7. We report 3 pediatric cases of AA with normal cytogenetics followed by acquisition of monosomy 7. Bone marrow biopsies were initially diagnostic of AA but later showed monosomy 7 and an increased number of megakaryocytes with small hypolobated nuclei. Immunohistochemical stains for CD61 highlighted the marked dysmegakaryocytopoiesis. The marrow blast percentage was increased in only 1 patient with 4.6% blasts. The 3 patients underwent bone marrow transplantation, and each has remained disease free for 7 to 18 months after transplantation. Pediatric patients with AA and normal cytogenetics may develop monosomy 7 with a myelodysplastic syndrome, unclassified. Patients with AA and monosomy 7 should be evaluated for dysmegakaryocytopoiesis.
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PMID:Aplastic anemia and monosomy 7-associated dysmegakaryocytopoiesis. 1707 89

Acute myeloid leukaemia (AML) with multilineage dysplasia (MD) is one of the four main categories of AML in the World Health Organization (WHO) classification. The role of bone marrow trephine biopsy (BMTB) histology and immunohistochemistry in the diagnosis of AML-MD is currently unclear. BMTBs were studied in 11 cases of AML-MD and two cases of myelodysplasia that subsequently transformed to AML. Among them, six cases showed trilineage dysplasia and seven showed bilineage dysplasia. With respect to conforming to the WHO definition of AML, documentation of an increased proportion of immature myeloid cells was possible on morphology and counting of immature cells following immunostaining with CD34, CD117 or HLA-DR antibodies. Recognition and quantification of dysplastic features in the haemopoietic lineages was made easier by immunohistochemistry with antibodies to ret40f (glycophorin C), myeloperoxidase, CD61 and/or CD42b, CD34, CD117 and HLA-DR. Based on this relatively small series of cases we show the utility of BMTB and immunohistochemistry as an aid to the diagnosis of AML-MD. This has to be seen not just in light of its utility at diagnosis, but also the role the diagnostic BMTB would play for purposes of comparison when follow-up BMTBs are submitted in this group of patients.
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PMID:Bone marrow trephine findings in acute myeloid leukaemia with multilineage dysplasia. 1797 48

A 16-month-old female spayed Labrador Retriever was referred to the University of Edinburgh for exercise intolerance, inappetence, and severe anemia. A CBC showed severe nonregenerative anemia and moderate numbers of atypical cells with morphologic features most consistent with megakaryoblastic origin. Similar cells were identified in a bone marrow aspirate and accounted for 23% of all nucleated cells. Atypical promegakaryocytes and megakaryocytes were also noted. Myelodysplastic syndrome affecting the megakaryocytic lineage was suspected. Cytologic examination of a fine-needle aspirate of the spleen revealed rare megakaryoblasts similar to those in blood and bone marrow. At necropsy, the bone marrow consisted of atypical megakaryoblasts and megakaryocytes that were also infiltrating spleen, liver, lymph nodes, renal perihilar tissue, and visceral adipose tissue, consistent with acute megakaryoblastic leukemia. Immunohistochemical analysis of splenic sections confirmed megakaryoblastic origin (immunoreactive for CD61 and von Willebrand factor). Some leukemic cells were also immunoreactive for myeloperoxidase (MPO). This aberrant immunophenotype suggested both megakaryocytic and granulocytic/monocytic differentiation of the leukemic cells. To our knowledge, this is the first report of MPO-positive acute megakaryoblastic leukemia in a dog.
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PMID:Myeloperoxidase-positive acute megakaryoblastic leukemia in a dog. 2209 89


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