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

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

We investigated 23 patients for their chimerism status who underwent allogeneic transplantation using peripheral blood progenitor cells (PBPCT) for chronic myelogenous leukemia (CML) (n = 14), acute myelogenous leukemia (AML) (n = 5), acute lymphoblastic leukemia (n = 1), myelodysplasia (MDS) (n = 1), and Hodgkin's disease (HD) (n = 2). These data were compared with those of patients after allogeneic BMT after matching them for disease and disease stage, sex of donor and recipient, GVHD prophylaxis, conditioning therapy and degree of HLA disparity. Patients were studied monthly up to 16 months post-transplant. In 11 of 23 (48%) patients who were transplanted with PBPCs and in 18 of 23 (78%) patients after BMT a mixed chimerism was detected at 1 month post-transplant. After 3 months, six of 21 (29%) evaluable patients after PBPCT remained mixed chimeric as opposed to 12 of 21 (57%) patients after BMT. We also assessed minimal residual disease using detection of the chimeric BCR/ABL transcripts by PCR of CML patients in this study. In four of 14 (29%) patients who underwent PBPCT, the BCR/ABL chimeric transcript was detected, while after BMT eight of 14 (57%) CML patients remained BCR/ABL positive. In two of these BMT patients, a cytogenetic relapse developed subsequently, and one other patient suffered a hematological relapse, whereas one of the CML patients relapsed after PBPCT. The present data may indicate that after PBPCT the incidence of leukemic relapse is similar or even lower than after BMT.
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PMID:Molecular studies of chimerism and minimal residual disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation. 886 52

New treatments which may change the course of a disease, or which have potential carcinogenicity, may result in the development of new cytogenetic or clinical disorders. Three patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia (CML) who developed new cytogenetic abnormalities after achieving a cytogenetic complete remission (CR) of their Ph-positive disease with interferon alpha (IFN-alpha) based therapy are described. Patient 1 developed chromosomal abnormalities involving chromosomes 5 (5q13-34) and later 7 (monosomy 7) 60 months after the start of therapy and 20 months after IFN-alpha was discontinued. A myelodysplastic syndrome was noted 83 months from the start of therapy. Patient 2 developed a myeloproliferative syndrome with 18p11 chromosomal abnormalities 90 months after the start of the therapy and 60 months after IFN-alpha was discontinued. Patient 3 developed a chromosome 11 abnormality (11q21-23) 23 months after the start of therapy, without hematological manifestations. All three patients remain in cytogenetic CR of Ph-positive disease with the hypermetaphase fluorescent in situ hybridization and polymerase chain reaction studies for BCR/ABL showing minimal residual disease. The emergence of new cytogenetic or clinical disorders in patients with CML on IFN-alpha therapy needs to be monitored. These findings may be related to changing the natural course of CML, to therapy, or to the emergence of suppressed clones in a stem cell disorder.
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PMID:Emergence of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases. 918 Mar 6

Late clonal complications of aplastic anemia (AA) such as acute leukemia, myelodysplastic syndromes or paroxysmal nocturnal hemoglobinuria have been recognized for a long time. To our knowledge, chronic myelogenous leukemia (CML) as a late complication of severe aplastic anemia has as yet not been reported. We report here a case of AA treated successfully with antilymphocytic globulin and cyclosporin in whom Ph1 negative, BCR/ABL negative CML developed 8 years after diagnosis of AA. This case of atypical, secondary CML was refractory to treatment with interferon alpha and hydroxyurea.
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PMID:Atypical chronic myelogenous leukemia following immunosuppressive therapy for severe aplastic anemia. 1051 77

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

Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. In 2-10% of the cases, this chimeric gene is generated by variant rearrangements, involving 9q34, 22q11, and one or several other genomic regions. All chromosomes have been described as participating in these variants, but there is a marked breakpoint clustering to chromosome bands 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, 17q21, 17q25, 19q13, 21q22, 22q12, and 22q13. Despite their genetically complex nature, available data indicate that variant rearrangements do not confer any specific phenotypic or prognostic impact as compared to CML with a standard Ph chromosome. In most instances, the t(9;22), or a variant thereof, is the sole chromosomal anomaly during the chronic phase (CP) of the disease, whereas additional genetic changes are demonstrable in 60-80% of cases in blast crisis (BC). The secondary chromosomal aberrations are clearly nonrandom, with the most common chromosomal abnormalities being +8 (34% of cases with additional changes), +Ph (30%), i(17q) (20%), +19 (13%), -Y (8% of males), +21 (7%), +17 (5%), and monosomy 7 (5%). We suggest that all these aberrations, occurring in >5% of CML with secondary changes, should be denoted major route abnormalities. Chromosome segments often involved in structural rearrangements include 1q, 3q21, 3q26, 7p, 9p, 11q23, 12p13, 13q11-14, 17p11, 17q10, 21q22, and 22q10. No clear-cut differences as regards type and prevalence of additional aberrations seem to exist between CML with standard t(9;22) and CML with variants, except for slightly lower frequencies of the most common changes in the latter group. The temporal order of the secondary changes varies, but the preferred pathway appears to start with i(17q), followed by +8 and +Ph, and then +19. Molecular genetic abnormalities preceding, or occurring during, BC include overexpression of the BCR/ABL transcript, upregulation of the EVI1 gene, increased telomerase activity, and mutations of the tumor suppressor genes RB1, TP53, and CDKN2A. The cytogenetic evolution patterns vary significantly in relation to treatment given during CP. For example, +8 is more common after busulfan than hydroxyurea therapy, and the secondary changes seen after interferon-alpha treatment or bone marrow transplantation are often unusual, seemingly random, and occasionally transient. Apart from the strong phenotypic impact of addition of acute myeloid leukemia/myelodysplasia-associated translocations and inversions, such as inv(3)(q21q26), t(3;21)(q26;q22), and t(15;17)(q22;q12-21), in CML BC, only a few significant differences between myeloid and lymphoid BC are discerned, with i(17q) and TP53 mutations being more common in myeloid BC and monosomy 7, hypodiploidy, and CDKN2A deletions being more frequent in lymphoid BC. The prognostic significance of the secondary genetic changes is not uniform, although abnormalities involving chromosome 17, e.g., i(17q), have repeatedly been shown to be ominous. However, the clinical impact of additional cytogenetic and molecular genetic aberrations is most likely modified by the treatment modalities used.
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PMID:Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. 1191 88

Mutations in signal transduction molecules, which regulate cell differentiation and proliferation, are involved in the development of leukemia. Aberrations of receptor type tyrosine kinases are known to arise from FLT3 mutations in acute myeloid leukemia (AML) and myelodysplastic syndrome, and c-Kit mutations in mast cell tumors. BCR/ABL found in chronic myelogenous leukemia (CML) is a hallmark of the constitutively active forms of cytoplasmic tyrosine kinases. Downstream of the tyrosine kinase is the RAS GTP-binding protein, and genetic mutations related to this protein have been found in a wide variety of malignant tumors including hematopoietic tumors. In the nucleus, transcription factor-encoding genes are frequently detected as the targets of chromosomal translocations found in specific types of leukemias. For instance, the AML1 gene generates AML1/MTG8 chimera by t (8;21) translocation in AML (M2), AML1/EVI-1 chimera by t (3;21) translocation in blastic crisis of CML, and TEL/AML1 chimera in t (12;21) translocation (pre-B cell type acute lymphoblastic leukemia). Another example of abnormal transcription factors is PML/RAR alpha generated by t (15;17) translocation found in acute promyelocytic leukemia. Mutations or deletions of tumor suppressor genes are frequently found in cell cycle regulators such as p53, RB and p16 genes. Therefore, mutations of any molecules involved in the signal transduction pathways from growth factor receptors to inside the nucleus are thought to contribute to neoplastic transformation of hematopoietic cells.
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PMID:[Molecular mechanisms in leukemogenesis]. 1214 88

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

We describe a rare case of myelodysplastic syndrome that developed chronic myelogeneous leukemia with acquisition of Philadelphia chromosome. The major BCR/ABL transcript was confirmed by molecular analysis. Shortly thereafter, the patient showed transformation to blastic crisis. Hematological remission was achieved after 3 months of treatment with imatinib mesylate. The patient relapsed with additional chromosomal abnormalities and the disease became refractory to the treatment. Acquisition of the Philadelphia chromosome is an infrequent event in myelodysplastic syndrome, and the addition of this change to the initial genetic abnormality that caused MDS may have been associated with the accelerated clinical course of this patient.
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PMID:A case of myelodysplastic syndrome developed blastic crisis of chronic myelogenous leukemia with acquisition of major BCR/ABL. 1289 86


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