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

This study concerns a patient with minor (m)-BCR/ABL transcript-positive and Philadelphia (Ph) chromosome-negative myelodysplastic syndrome (MDS). The patient was a 78-year-old man whose condition was diagnosed as refractory anemia with excess of blasts in transformation. Molecular genetic studies, using reverse transcriptase polymerase chain reaction analysis detected m-BCR/ABL messenger RNA. We used spectral karyotyping to analyze metaphase cells but could not detect a Ph chromosome. Fluorescence in situ hybridization, however, revealed fusion signals of BCR and ABL probes on an apparently normal chromosome 22.
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PMID:A variant form of myelodysplastic syndrome with Ph- minor-BCR/ABL transcript. 1153 Aug 6

Chronic myeloid leukemia(CML) is a generic term that includes five subtypes; i.e. chronic granulocytic leukemia(CGL) (95% of all CML, 90% are Ph+, 5% are Ph-, BCR/ABL+), atypical CML(survival is worse than that of CGL), chronic myelomonocytic leukemia(a subtype of myelodysplastic syndrome), chronic neutrophilic leukemia (Ph-, BCR/ABL-) and juvenile CML(Ph-, BCR/ABL-). It is not so easy to make a diagnosis of Ph-negative CML. Also, about 25% of adult acute lymphoid leukemia(ALL) patients and some essential thrombocythemia patients have Ph chromosome. In addition, about a half of cases with Ph-positive ALL have the same size of BCR/ABL fusion protein as that in Ph-positive CML. It is necessary to distinguish them by the distinctive morphological, cytogenetical and immunological characteristics of these diseases.
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PMID:[Differential diagnosis of chronic myeloid leukemia and the related disorders]. 1176 39

Chromosome rearrangements affecting band 3q21, namely, the inv(3)(q21q26), the t(3;3)(q21;q26), and the t(1;3)(p36;q21), are associated with a particularly poor prognosis in myeloid leukemia or myelodysplasia. Originally, inv(3) and t(3;3) breakpoints have been reported to cluster in a region (breakpoint cluster region, BCR) of approximately 30 kb, which is located centromeric and downstream of the ribophorin I (RPN-I) gene. More recently, we established a PAC contig that includes the 3q21 BCR, and used these PAC clones to map breakpoints in patient samples by both metaphase and interphase fluorescence in situ hybridization (FISH) analysis. A significant proportion of inv(3) and t(3;3) breakpoints was located at sometimes considerable distances centromeric of the originally described BCR, in a region recently also implicated in t(1;3) rearrangements. These breakpoints may thus define a second, centromeric BCR (BCR-C), or extend the original 3q21 BCR to a size of approximately 100 kb. Activation of the EVI-1 gene in 3q26 by regulatory sequences of the housekeeping gene RPN-I has been suggested as a leukemogenic mechanism in patients with inv(3) and t(3;3). However, despite a number of characteristics that make EVI-1 an attractive candidate oncogene, its biological properties fail to fully explain the phenotype of leukemias carrying 3q rearrangements. Several additional candidate genes have been identified in or near the 3q21 breakpoint region, but their possible contribution to the characteristics of leukemias with 3q21 rearrangements remains to be explored.
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PMID:Rearrangements of chromosome band 3q21 in myeloid leukemia. 1190 37

Acquired reciprocal chromosomal translocations that involve chromosome bands 5q31-33 are associated with a significant minority of patients with BCR-ABL-negative chronic myeloid leukemias. The most common abnormality is the t(5;12)(q33;p13), which fuses the ETV6/TEL gene to the platelet-derived growth factor receptor-beta (PDGFRB), a receptor tyrosine kinase that maps to 5q33. PDGFRB is disrupted by other translocations and to date four additional partner genes (H4, HIP1, CEV14 and Rab5) have been reported. Clinically, most patients present with a myeloproliferative disorder (MPD) with eosinophilia, eosinophilic leukemia or chronic myelomonocytic leukemia and thus fall into the broader category of myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS). With the advent of targeted signal transduction therapy, patients with rearrangement of PDGFRB might be better classified as a distinct subgroup of MPD/MDS.
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PMID:Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta. 1191 93

We report a case of atypical chronic myeloid leukemia who showed leukocytosis with immature granulocytes and dysplastic features but no monocytosis or basophilia. Cytogenetic analysis by conventional G-banding showed an abnormal clone, which was interpreted as 46,X,-Y,+der(?)t(?;1)(?;q?1), and no Philadelphia chromosome. Reverse transcription-polymerase chain reaction did not show either major or minor BCR-ABL chimeric mRNA. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) refined the karyotype to 46,X,der(Y)t(Y;1)(q11.1 or.2;q12). The der(Y)t(Y;1) abnormality was reported previously in 9 cases and associated with myelodysplastic syndrome or chronic myeloproliferative disorders. SKY in combination with the standard banding method and FISH may be useful for exploring undefined chromosome abnormalities in hematological disorders.
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PMID:Spectral karyotyping refined the identification of a der(Y)t(Y;1)(q11.1 or.2;q12) in the blast cells of a patient with atypical chronic myeloid leukemia. 1205 51

We report a late appearance of the Philadelphia chromosome (Ph) with the p190 BCR/ABL chimeric transcript in a 69-year-old patient with acute myelogenous leukemia (AML) that had evolved from myelodysplastic syndrome (MDS). In July 1997, the patient was found to have pancytopenia caused by refractory anemia with excess of blasts, which evolved into AML in 4 months. The leukemic cells were positive for CD13, CD14, CD33, and HLA-DR and had a normal karyotype. The patient achieved a complete remission after combination chemotherapy. However, his leukemia relapsed in November 1999, with the appearance of leukemic cells positive for CD7, CD13, CD34, and HLA-DR with a 46, XY, add (18) (p11) karyotype. The patient failed to achieve the second remission after several courses of intensive chemotherapy. When the number of blastic cells, showing the same surface phenotypes, in the peripheral blood increased drastically in April 2000, chromosomal analysis of leukemic cells revealed a 46, XY, t(9;22) (q34;q11), add(18)(p11) karyotype. The fusion of the BCR and ABL genes was confirmed by fluorescence in situ hybridization analysis, and the reverse transcription-polymerase chain reaction analysis further revealed the presence of the p190 BCR/ABL chimeric transcript. The appearance of the Ph chromosome in the course of MDS transforming to AML is very rare and may be correlated to the disease progression.
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PMID:[Late appearance of Philadelphia chromosome with the p190 BCR/ABL chimeric transcript in acute myelogenous leukemia progressing from myelodysplastic syndrome]. 1278 57

Cancer is also an epigenetic disease. The main epigenetic modification in humans is DNA methylation. Transformed cells undergo a dramatic change in their DNA methylation patterns: certain CpG islands located in the promoter regions of tumor-suppressor genes become hypermethylated and the contiguous gene rests silenced and this phenomenon occurs in an overall genomic environment of DNA hypomethylation. The profile of CpG island hypermethylation in hematologic malignancies is an epigenetic signature unique for each subtype of leukemia or lymphoma. Although the most widely studied genes are the cell-cycle inhibitors p15INK4b and p16INK4a (specially in AML and ALL), the list of methylation-repressed genes in these neoplasms is expanding very rapidly, including MGMT, RARB2, CRBP1, SOCS-1, CDH1, DAPK1, and others. A necessary cross-talk between genetic alterations and DNA methylation exists: certain chromosomal translocations may induce hypermethylation, such as the PML-RARa, or attract methylation, such as BCR-ABL, but DNA hypomethylation can be the culprit behind the genesis of certain abnormal recombination events. From a translational standpoint, hypermethylation can be used as a marker of recurrent disease or progression, for example, in MDS, or response to chemotherapy, such as MGMT methylation in B-cell non-Hodgkin's lymphoma. Furthermore, promising studies using DNA demethylating agents and histone deacetylase inhibitors are underway to awake these dormant tumor-suppressor genes for a better treatment of the patient with a hematologic malignancy.
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PMID:Profiling aberrant DNA methylation in hematologic neoplasms: a view from the tip of the iceberg. 1458 79

Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the hematopoietic stem cell. Four different entities are defined: chronic myeloid leukemia (CML), polycythemia vers, essential thrombocythaemia, and idiopathic myelofibrosis. In addition, overlapping entities within the CMPDs and between CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are performed to classify the subtype exactly and to assess risk factors and prognosis. Cytogenetic and molecular analyses are mandatory for the characterization of the malignant clone. Hydroxyurea and interferon-alpha have proven effective in all CMPE. In CML, specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates. Allogeneic stem cell transplantation is the only curative treatment option for all entities. In CML, the decision-making analysis should be based on established scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should only be performed in patients with unfavorable prognosis.
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PMID:[Chronic myeloproliferative diseases. Diagnosis and therapy]. 1467 16

Targeted therapies for hematological malignancies have come of age since the advent of all trans retinoic acid (ATRA) for treating APL and STI571/Imatinib Mesylate/Gleevec for CML. There are good molecular targets for other malignancies and several new drugs are in clinical trials. In this review, we will concentrate on individual abnormalities that exist in the myelodysplastic syndromes (MDS) and myeloid leukemias that are targets for small molecule therapies (summarised in Fig. 1). We will cover fusion proteins that are produced as a result of translocations, including BCR-ABL, the FLT3 tyrosine kinase receptor and RAS. Progression of diseases such as MDS to secondary AML occur as a result of changes in the balance between cell proliferation and apoptosis and we will review targets in both these areas, including reversal of epigenetic silencing of genes such as p15(INK4B).
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PMID:Targeted therapies in myeloid leukemia. 1475 35

We conducted a retrospective study to define the significance of Philadelphia chromosome (Ph) in myelodysplastic syndrome and acute leukemia in the adults at this institution and the literature was reviewed. One hundred forty-eight cases of t(9;22)(q34;q11) were identified for the period September 1993 through August 2001. The presentation of 124 cases (84%) was that of typical CML in chronic phase. Nineteen cases (13%) presented as de novo ALL, two cases (1%) presented as de novo AML and three cases (2%) presented as myelodysplastic syndrome (MDS). The estimated incidences of t(9;22)(q34;q11) in ALL and AML are 21 and 0.6%, respectively. Ph+ AMLs are increasingly being reported with either M-BCR or m-BCR gene rearrangements, similar to those found with Ph+ ALL lending support to the notion that Ph+ AMLs are distinct entities and not merely blastic phases of undiagnosed CML. This is further supported by the existence of Ph+ MDS cases.
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PMID:Philadelphia chromosome positive myelodysplastic syndrome and acute myeloid leukemia-retrospective study and review of literature. 1512 Sep 28


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