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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We treated a 16-month-old girl with myelodysplastic syndrome (MDS; refractory anemia with excess of blasts subtype, RAEB by FAB classification) that developed into acute megakaryoblastic leukemia (ANLL-M7). The blast cells were positive for CD41 shown by flow cytometry and for platelet peroxidase by electron microscopy. Cytogenetically, five kinds of abnormal karyotypes were apparent at the initial visit and karyotypic progression (clonal evolution) was also evident. These karyotypes were considered to be derived from the putative original clone, 48,XX, +6, +21. The observed karyotypes were considered 50,XX, +4,add(4)(q31), +6,add(7)(p22),add(10)(q24),add(12)(q11), +20, +21, + mar[karyotype A];48,XX,add(4)(q31), +6,add(10)(q24),add(12)(q11), +21 [karyotype B];48,XX, +6,t(6;13)(p23;q14), +21 [karyotype C];51,XX, +X, t(6;13)(p23;q14), + der(6)t(6;13)(p23;q14), +21, +21, + mar [karyotype D]; and 49,XX, +X, -3,t(6;13)(p23;q14), +der(6)t(6;13)(p23;q14), -12, +21, +21, + mar [karyotype E]. It seems karyotypes B and C were derived from the putative clone; karyotype B developed into karyotype A; and karyotype C developed into karyotype E through karyotype D. After development of ANLL-M7, the cytogenetic study showed a karyotype with further karyotypic progression. The patient was treated with high-dose cytosine arabinoside (HD AraC) followed by allogeneic bone marrow transplantation. Despite intensive care, she died 3 months after the transplantation.
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PMID:Childhood myelodysplastic syndrome with clonal evolution progressing to acute megakaryoblastic leukemia (ANLL-M7). 822 7

When purified control neutrophils were primed with GM-CSF, a significant increase in FMLP-induced MPO release was observed (mean +/- S.E.M., 3.4 +/- 0.8 mU/10(7) unprimed cells compared to 6.5 +/- 1.1 mU/10(7) primed cells, p < 0.001). This MPO release was greatly augmented by Cytochalasin B (Cy B), but after the addition of Cy B the priming effects of GM-CSF became less obvious. Exposure to GM-CSF without FMLP did not enhance MPO release. Within whole blood, FMLP produced negligible MPO release, but priming with GM-CSF prior to FMLP always resulted in a significant increase in MPO release. Myelodysplastic neutrophils released similar amounts of MPO in response to FMLP, compared with control cells (3.4 +/- 0.8 mU/10(7) control cells compared to 2.7 +/- 0.3 mU/10(7) MDS cells, p > 0.05). Priming with GM-CSF produced an increase in FMLP-stimulated MPO release comparable with control cells. In terms of total MPO content, although some MDS patients exhibited low levels, as a group there was no significant difference from controls (169 +/- 21 mU/10(7) control cells compared with 157 +/- 19 mU/10(7) MDS cells). These findings suggest that MPO activity is not a universal defect in MDS and cannot account for the defects in respiratory burst activity in these neutrophils.
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PMID:The effects of GM-CSF on myeloperoxidase release in normal and myelodysplastic neutrophils. 824 7

A 78 year old female was found to have pancytopenia in February 1991. Bone marrow was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A diagnosis of MDS (RAEB) was made and she was treated with transfusions and ubenimex. Leukemic transformation was noted in July. On Admission in October 1991, her laboratory examinations revealed the following: WBC 38,900/microliters with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light microscopy, but were positive by electron microscopy. Surface marker for CD13 was positive. These findings corresponded to M0 of the FAB subtype. Chromosome analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells examined, Southern analysis showed the rearrangement of the break point cluster region (bcr). Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr/abl mRNA. She was treated with transfusions and methyl-prednisolone. Her blast counts declined and Ph1 chromosome was only positive in 1 of 12 metaphases examined. She died of pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have previously been reported. The observations indicate that Ph1 chromosome positive acute leukemias were heterogenous in nature.
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PMID:[RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major cluster region]. 825 8

Mutation of the ras oncogenes is the most commonly detected molecular abnormality in acute myelogenous leukemia and myelodysplastic syndromes (MDS). This molecular event may either be acquired by different subclones or by all malignant cells. The availability of the ras p21 monoclonal antibody Y13 259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. The bone marrow smears from 41 patients with MDS were analysed by two independent observers after treatment with MoAb Y13 259, biotinylated goat antirat IgG, streptavidin, peroxidase and staining with diaminobenzidine. A high proportion of strongly positive smears was found among patients with MDS. This positivity was found in 25% of refractory anemia, in 80% of the refractory anemias with excess of blasts, and in 90% of those in transformation, while all 7 cases with chronic myelomonocytic leukemia were found positive. The percentage of positivity may suggest that activation of ras oncogene in associated with disease progression.
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PMID:Analysis of immunohistochemical results of the ras oncogene product p21 in myelodysplastic syndromes. 835 32

The authors describe a case of chronic myelomonocytic leukemia in which a myeloperoxidase (MPO) deficiency of circulating monocytes was first detected by automated differential cell counting, and subsequently confirmed by cytochemical and immunocytochemical investigations. MPO activity in neutrophil granulocytes from the same case was found to be normal. MPO deficiency in monocytes appeared to be associated with impaired phagocytic capacity and, based on the results of immunophenotypic and ultrastructural studies, was most likely attributable to a partial maturation arrest of monocytes. The present case suggests that MPO deficiency in myelodysplastic syndromes may have its origin in a number of different pathogenetic mechanisms.
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PMID:Selective involvement of monocytes by acquired myeloperoxidase deficiency in a case of chronic myelomonocytic leukemia. 838 5

The mRNA expression of alkaline phosphatase (ALP), myeloperoxidase (MPO), defensin and G-CSF receptor (G-CSFR) in bone marrow cells of normal individuals and myeloid disorders, with or without in vitro stimulation by myeloid cell growth factors, i.e. G-CSF, GM-CSF and IL-3, were examined as markers for myeloid cell differentiation in both mononuclear cell (MNC) and polymorphonuclear cell (PMN) fractions. Without any stimulation, ALP mRNA was expressed only in PMNs, G-CSFR mRNA in PMNs were expressed stronger than in MNCs; both MPO and defensin mRNA were expressed to the same degree in both fractions. With stimulation, the ALP mRNA expression in both fractions was strongly enhanced by G-CSF, but the expression was inhibited by GM-CSF and/or IL-3. MPO mRNA expression was stimulated by G-CSF and/or GM-CSF in MNCs. G-CSFR mRNA expression was enhanced by G-CSF in both fractions. Defensin mRNA expression was inhibited by G-CSF. In cases of myelodysplastic syndrome and chronic myelogenous leukaemia which display a suppressed maturation of myeloid cells, our results demonstrated an almost normal response to these growth factors. Our results suggest that studies on these myeloid marker mRNA expressions would provide more knowledge about the differentiation state and cytokine reactivity of myeloid cells in normal individuals as well as various disorders.
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PMID:Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase, defensin and granulocyte colony-stimulating factor receptor mRNA expression in haemopoietic cells of normal individuals and myeloid disorders. 856 17

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.
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PMID:Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections. 857 29

We describe a patient with primary myelodysplastic syndrome (MDS) evolving into acute nonlymphocytic leukemia (ANLL) who had two cytogenetically unrelated abnormal clones. A 68-year-old man presented with refractory anemia with excess of blasts (RAEB) and developed overt ANLL. Two cytogenetically independent clones, one with 5q- and the other with 20q-, were observed when the patient developed ANLL. The clones carrying both 5q- and 20q- were not detected. Leukemic blast cells were positive for peroxidase, naphtol ASD chloroacetate esterase, CD13, CD33, CD34 and HLA-DR, but negative for alpha-naphthyl butyrate esterase, CD14, CD10, CD19, CD20, CD1, CD2, CD3, CD5 and CD7. Although there have been a few reports describing the presence of multiple cytogenetically unrelated clones in one patient with MDS, this is the first case report that the 5q- and 20q- anomalies are derived from independent clones.
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PMID:Two karyotypically unrelated clones with 5q- and 20q- in a primary myelodysplastic syndrome patient evolving into acute nonlymphocytic leukemia. 859 Jul 73

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.
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PMID:Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome. 861 53

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.
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PMID:Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis. 862 74


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