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

It has been shown that a 600 bp long cluster of cell lineage specific hypomethylated sites in the major breakpoint cluster region (M-bcr) on chromosome 22 exists in hematopoietic cells. To determine possible relationships between methylation patterns within the M-bcr and the stage of hematopoietic cell development, the M-bcr methylation status of 39 patients with leukemia and lymphoma and two patients with myelodysplastic syndrome with non-rearranged M-bcrs was examined by BgIII-HpaII digestion. In the myeloid malignancies, the presence of a hypermethylated 4.8 kb BgIII-BgIII M-bcr allele was directly proportional to the combined myeloblast and promyelocyte percentage of the specimen, whereas the presence of a 2.5 kb BgIII-HpaII allele was directly proportional to the combined percentage of monocytic cells and neutrophils. All five acute monoblastic leukemias showed a methylation pattern that closely resembled neutrophils. All of thirteen surface immunoglobulin positive B-cell malignancies showed a distinct methylation pattern consisting of three or more BgIII-HpaII restriction fragments of 2.5 kb or less in length. The B-cell precursor leukemias showed heterogeneous M-bcr methylation patterns, with four of seven showing a B-cell pattern and three showing a hypermethylated pattern with 4.8, 3.1/3.0 and/or 2.5 kb BgIII-HpaII M-bcr alleles. It is concluded that the M-bcr methylation status is related to the maturation of the neutrophil series; the surface immunoglobulin positive B-cell malignancies are characterized by a distinct, extreme hypomethylation pattern of the M-bcr; and the B-cell precursor malignancies appear to have a heterogeneous M-bcr methylation pattern.
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PMID:Methylation status of the major breakpoint cluster region in Philadelphia chromosome negative leukemias. 134 43

A human yeast artificial chromosome (YAC) library was screened by polymerase chain reaction with oligonucleotide primers defined for DNA sequences of the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erbB-2. Alu-PCR-generated human DNA sequences were obtained from the respective YAC clones and used for fluorescence in situ hybridization experiments under suppression conditions. After chromosomal in situ suppression hybridization to GTG-banded human prometaphase chromosomes, seven of nine initially isolated YAC clones yielded strong signals exclusively in the chromosome bands containing the respective genes. Two clones yielded additional signals on other chromosomes and were excluded from further tests. The band-specific YACs were successfully applied to visualize specific structural chromosome aberrations in peripheral blood cells from patients with myelodysplasia exhibiting del(5)(q13q34), chronic myeloid leukemia and acute lymphocytic leukemia with t(9;22)(q34;q11), acute promyelocytic leukemia (M3) with t(15;17)(q22;q21), and in a cell line established from a proband with the constitutional translocation t(3;8)(p14.2;q24). In addition to the analysis of metaphase spreads, we demonstrate the particular usefulness of these YAC clones in combination with whole chromosome painting to analyze specific chromosome aberrations directly in the interphase nucleus.
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PMID:Metaphase and interphase cytogenetics with Alu-PCR-amplified yeast artificial chromosome clones containing the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erbB-2. 156 26

Two cases of unclassified chronic myeloproliferative disorders (UCMPD), diagnosed by hematological, cytogenetic and DNA analyses, are described. Case 1: a 63 year old female was admitted because of leukocytosis (96,800/microliters) and splenomegaly. Hematological examinations revealed an increase of the granulocytes in the peripheral blood and bone marrow. The neutrophil alkaline phosphatase (NAP) score was 121. The patient developed blast crisis after 12 months of the chronic phase. Case 2: a 48 year old male was presented with fever and leukocytosis (20,000/microliters). Hematological examinations revealed an increase of granulocytes in the peripheral blood and bone marrow. The NAP score was 33. Maturation-arrest in granulocytic series and morphological abnormalities of marrow cells were not observed in the two cases. Cytogenetic analysis of bone marrow cells disclosed 46, XX, i (17 q) in case 1 and 47, XY, +8 in case 2. Southern blot analysis using 3' bcr probe and TransProbe-1 showed no bcr rearrangement. These cases are thought to be valuable in order to clarify the relationship between UCMPD and CMPD such as Ph1 negative chronic myelocytic leukemia and myelodysplastic syndromes.
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PMID:[Two cases of unclassified chronic myeloproliferative disorders]. 160 19

Diagnosing chronic myeloproliferative disorders (CMPD) can be difficult because of overlap and possible transitions between the different conditions and their similarity to reactive myeloproliferations. DNA analysis was applied to improve differentiation of CMPDs. All subtypes of CMPD analyzed, including chronic myeloid leukemia, agnogenic myeloid metaplasia, polycythemia vera, and essential thrombocythemia, had in common that granulocytes and bone marrow cells were clonal in origin, as shown by X chromosome-linked DNA polymorphism in conjunction with methylation patterns (n = 32). Reactive myeloproliferations, by contrast, showed polyclonal inactivation patterns. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome because the latter (n = 7) also exhibited clonal hematopoiesis. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 201) to detect bcr gene rearrangement. Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis. Chronic myeloproliferative disorders represent clonal hemopoietic diseases that probably have specific underlying genetic defects. Thus DNA analysis can aid substantially in the differential diagnosis of CMPD.
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PMID:DNA analysis to aid in the diagnosis of chronic myeloproliferative disorders. 161 25

Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS.
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PMID:[Myelodysplastic syndrome associated with marked eosinophilia and basophilia]. 163 67

We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.
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PMID:Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics. 146 36

The diagnosis and classification of leukaemia started with simple morphological examination and now embraces use of special stains, cytochemistry and immunophenotyping. Genetic studies have progressed from karyotyping to detection of genetic changes within genes. The methods described in this chapter are still at an early stage of development and, so far, have provided relatively little in the way of an extension of available diagnostic information. Sometimes the methods provide extensions to existing techniques, for example by the detection of bcr rearrangements in patients who have CML or ALL but do not have a detectable Philadelphia chromosome. Another example is retrospective diagnosis of gene rearrangements using DNA from slide preparations. However, it should be noted that it has only very recently been shown that there is likely to be a causal relationship between the Ph chromosome and leukaemia. Daley et al (1990) induced CML in mice by bone marrow transplantation of cells infected with a retrovirus encoding P210bcr/abl and Heisterkamp et al (1990) produced mice transgenic for a BCR/ABL P190 DNA construct and showed that the progeny died of acute leukaemia (mostly ALL). We have not summarized studies of the incidence of activated oncogenes such as RAS in leukaemia and myelodysplasia. Such oncogenes appear to be involved in many tumours and may well indicate either a predisposition to cancer or a particular stage of malignancy, but their analysis does not at present help in making a diagnosis. It is likely that, as we understand more about the nature of the malignant process, we shall be able to use genetic techniques to enhance considerably both diagnostic and prognostic precision.
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PMID:Molecular biology and leukaemia diagnosis. 227 97

Chronic myeloid leukemia consists of Philadelphia chromosome positive disease in 90% of cases, and a further 5%, although Philadelphia chromosome negative, exhibit bcr gene rearrangements consistent with the disease. The remaining 5% of cases have a heterogeneous clinical picture with a course unlike that of classical chronic myeloid leukemia, and may belong to different pathologic entities. We report five cases belonging to the latter group, initially identified as Philadelphia chromosome negative, bcr non-rearranged chronic myeloid leukemia, that developed progressive leucocytosis, absolute monocytosis, myelodysplasia, extramedullary hematopoiesis, and had evidence of myelofibrosis. These cases may represent a distinct clinical entity characterized by neutrophilic myelofibrosis, which can be identified prospectively by clinical and pathologic criteria. Standard therapy for treating chronic myeloid leukemia or idiopathic myelofibrosis may not be appropriate for this group.
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PMID:Neutrophilic myelofibrosis presenting as Philadelphia chromosome negative BCR non-rearranged chronic myeloid leukemia. 232 6

A case of Philadelphia (Ph1) chromosome positive acute myelogeneous leukemia (AML) following a refractory anemia with excess of blasts (RAEB) with 8 trisomy is reported. The 80-year-old man developed pancytopenia during the course of follow-up after the surgical operation of the carcinoma of the sigmoid colon and the rectum for which no irradiation therapy nor chemotherapy had been applied. The diagnosis of RAEB was made according to the diagnostic criteria proposed by FAB co-operative group. Chromosomal analysis revealed 8 trisomy in 54% of the metaphases of bone marrow cells. The remainders showed normal karyotype without Ph1 chromosome. He was on androgenic steroid and activated Vitamin D3 without significant changes in the clinical and the hematological features until 3 months later when many atypical blasts appeared in the peripheral blood. The diagnosis of AML (M2) was made. Chromosomal analysis revealed Ph1 chromosome with the typical 9;22 translocation in 100% of the examined cells. 8 trisomy was not detected any more. Southern blot analysis using bcr probe showed bcr rearrangement. He was treated with a small doses of Ara-C. There was some reduction in the number of blasts in the peripheral blood. However, he died of septicemia 2 months later. The present case indicates that Ph1 positive acute leukemia with bcr rearrangement is not necessarily considered as a blastic transformation of chronic myelogeneous leukemia and such a cytogenic abnormality can appear in a leukemic transformation of myelodysplastic syndrome.
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PMID:[Acquisition of Philadelphia chromosome with bcr rearrangement concomitant with transformation of refractory anemia with excess of blasts with 8 trisomy into acute myelogenous leukemia]. 236 38

Results of our study on the activation of N-ras oncogene by point mutation in human leukemia and myelodysplastic syndrome have been described in this article. Point mutation was observed mainly on the 12th, 13th and 61st amino acid codon of ras genes. Therefore, oligomers containing mutations at these codons were used as probes for dot blot analysis of DNA derived from patient's bone marrow cells or leukemia cells. Polymerase chain reaction technique was used to amplify the DNA of ras genes containing 12th, 13th and 61st codons. By this technique, sensitivity of the method to detect the point mutations in ras oncogene was remarkably increased. Detection of the mutation in ras gene is considered to be very useful for the diagnosis, determination of remission and finding of relapse at an early stage. Study on the fused gene of bcr-abl, its mRNA and protein in chronic myelogenous leukemia is a good and reliable method to prove the existence of Ph1 positive chromosome by gene technology. Identification of the Ph1 acute lymphoblastic leukemia (ALL) has become possible by studying abl oncogene in Ph1 positive ALL. This method can be used also for the diagnosis of Ph1 ALL.
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PMID:[Oncogenes in human leukemia]. 265 Jun 33


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