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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent contributions from molecular biology, biotechnology and recombinant DNA applications have led to important clinical and therapeutic advances in chronic myelogenous leukemia (CML). Developments in the methodology of genetic investigation have clarified the molecular alterations brought about by the appearance of the Philadelphia chromosome. It is possible that the hybrid bcr/abl gene plays an important role in the pathogenesis of CML by subverting the mechanism of homeostasis through the uncoordinated activation of cell growth stimulating and regulating factors. Further improvements have been brought about by the polymerase chain reaction (PCR) which permits an indirect identification of the fusion gene and the study of minimal residual disease during remission after chemotherapy and bone marrow transplantation (BMT). Clinical trials have shown that alpha-interferon, alone or in association with chemotherapy, induces long term clinical and cytogenetic remission in those CML patients in whom BMT from either related or unrelated donors cannot be performed. Allogeneic BMT seems to be the treatment of choice in younger people. However, since a minority of subjects have HLA identical siblings, the possibility of using unrelated donors to provide long term disease free survival has been explored even if the availability of a compatible donor is the primary limiting factor. The development of in vivo and in vitro purging procedures has aroused new interest in autologous bone marrow transplantation. This procedure benefits particularly from biotherapeutic agents which selectively act on the marrow by suppressing bcr/abl positive cells.
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PMID:Chronic myelogenous leukemia: state of the art. 184 Aug 16

A case of chronic myelogenous leukemia (CML) is described whose leukemic cells appeared to contain two Philadelphia (Ph) chromosomes originating from different translocations involving the two chromosomes 22. The karyotype of the affected cells, established on two different occasions, was: 46,XY,t(9;22)(q34;q11),t(15;22)(p11;q11) with no normal chromosomes 22 and only one 9q+ in each of 115 marrow cells examined. The same findings were present in 50 peripheral blood cells cultured without phytohemagglutinin (PHA) stimulation. When stimulated with PHA, a normal male karyotype was present in the 11 cells examined. There were no additional chromosomal abnormalities and no indication of a blastic crisis after nearly 1 year following the original study. Analysis of the breakpoint cluster region (bcr) on chromosome 22 in the DNA of the affected cells (marrow) revealed evidence for one rearranged chromosome 22 and one normal chromosome 22, indicating that the t(15;22) was not due to the usual Ph translocation seen in CML. The results point to the crucial usefulness of molecular analysis in confirming cytogenetic results related to Ph translocations in CML.
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PMID:Molecular differentiation of two different translocations producing two apparent Ph chromosomes in a patient with CML. 188 59

Current induction therapies for acute and chronic leukemias and the lymphomas have achieved significant complete remission rates. Despite this initial success, disease recurrence remains a major problem. Relapse from clinically undetectable residual malignant cells is the most likely mechanism of recurrence. Of crucial importance to the clinician is the accurate detection of residual malignant cells prior to clinical relapse. Standard approaches to evaluate for this minimal residual disease (MRD) allow detection only when the malignant clone exceeds 1%. Patients in remission, however, may frequently have residual neoplastic cells that are far below this level. Recently, several investigators have adapted the polymerase chain reaction (PCR) to detect tumor-specific DNA or RNA sequences. This approach is highly sensitive (able to detect 1 malignant cell in 10(6) normal cells). The application of this technique to the study of MRD thus far has been limited to tumors in which specific DNA or RNA sequence data are available. This review describes the application of PCR to the detection of MRD in patients with chronic myelogenous leukemia, acute lymphoblastic leukemia, and follicular small cleaved cell lymphoma. Because the number of clinical studies and length of follow-up is limited, detection of MRD by PCR is at present largely a research tool and the biological significance of MRD as determined by PCR must await further studies.
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PMID:Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. 189 4

A 19-year-old man with Philadelphia-positive chronic myelogenous leukemia treated with interferon-alpha (IFN-alpha) therapy for 45 months had systemic lupus erythematosus disease features: malar rash, migratory arthralgias, elevated antinuclear antibodies, elevated antinative DNA, hypocomplementemia, lymphopenia, and proteinuria. After discontinuation of the IFN and initiation of corticosteroids, there was gradual recovery of symptoms, a decline in antinative DNA and antinuclear antibodies to normal levels, and a decrease in proteinuria. The potential association between IFN therapy and the development of systemic lupus erythematosus, and the role of IFN in other autoimmune diseases, is discussed.
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PMID:Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. 189 53

Southern blot analyses were performed in sequential DNA samples from 4 patients with Ph' + chronic myeloid leukaemia (CML) who underwent lymphoid or mixed blast crisis (BC). Genomic rearrangements at the breakpoint cluster region (bcr) and immunoglobulin heavy chain (IgH) gene level provided, in these cases, a sensitive and specific evaluation of response to therapy both in terms of blasts and Ph' + cell suppression. Recurrent BC was molecularly characterized in the 4 patients, showing each time identical individual specific DNA rearrangement patterns. Residual blasts were detected in 2 cases during intervening chronic phases by IgH rearrangements. Such findings highlight the specificity of these molecular markers, clearly indicating the failure of ablative therapy in eradicating the neoplastic clone. Finally, molecular and phenotypic identity in individual recurrent BC also suggested, in our cases, a lack of clonal evolution during disease progression.
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PMID:Chronic myeloid leukaemia lymphoid blast crisis. Relevance of molecular analysis at the bcr and immunoglobulin heavy chain gene level in monitoring response to therapy and residual disease. 190 Dec 72

We report a patient with chronic myeloid leukaemia (Philadelphia-positive with M-BCR rearrangement) in transformation whose blast cells had myelomonocytic morphology, absent terminal deoxynucleotidyl transferase expression and non-lymphoid cell surface markers (CD10-, CD19-, CD33+, CD14+, CD11+). Leukaemia cell DNA showed rearrangement of both immunoglobulin heavy chain and T-cell receptor delta genes. Such rearrangements may be a feature of a small proportion of patients with non-lymphoid transformation of CML as they are in a minority of cases of de novo acute non-lymphoblastic leukaemia.
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PMID:Non-lymphoid blast crisis of CML with rearrangement of immunoglobulin and T-cell receptor delta genes. 190 27

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.
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PMID:Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype. 191 41

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.
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PMID:Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia. 192 49

To characterize hematopoietic cells in mixed hematopoietic chimeras after allogeneic bone marrow transplantation (BMT), the authors examined the origin of progenies derived from hematopoietic progenitor cells of male recipients who received a marrow graft from female donors, by use of a Y-chromosome specific DNA (YDNA) probe in combination with an in vitro colony assay. Host-type hematopoietic cells were detected in cultured bone marrow mononuclear cells (BMMC) from 4 out of 6 patients studied, who were all in complete remission. In 2 patients of the mixed chimeras, the relative amount of host-derived YDNA from BMMC increased after methylcellulose cultures for 14 days. Analysis of individual colonies derived from granulocyte-macrophage colony forming units (CFU-GM) from these mixed chimeras, including 2 patients with chronic myelogenous leukemia (CML), revealed approximately 30% of total colonies were host-type, although no evidence for the existence of residual Ph1 positive cells was obtained by using polymerase chain reaction for detecting bcr-abl chimeric messenger RNA in the 2 CML patients. These findings provide direct evidence that considerable numbers of host-derived normal hematopoietic progenitors survive and persist for a long term in a certain population of marrow recipients, after BMT following supralethal radiochemotherapy.
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PMID:Origin of hematopoietic progenitor cells after bone marrow transplantation: analysis by means of a Y-chromosome specific DNA probe. 195 16

A case of Ph1+ chronic myeloid leukemia in blast crisis (CML-BC) is reported, in which the periodic acid Schiff and myeloperoxidase negative blasts displayed high terminal deoxynucleotidyl activity and coexpressed both B- (CD19, CD10, and CD24) and T- (CD7) lymphoid markers. In line with the immunophenotype, DNA analysis revealed a rearranged configuration of both the immunoglobulin and T-cell receptor (beta, gamma, and delta) genes. In spite of this dual B/T phenotype and genotype, the negativity of CyCD3 favors the suggestion that the target of the neoplastic event is an early B cell, with a cross lineage involvement of the putative common recombinase. However, taking into account that a normal counterpart of a biphenotypic B/T ALL has been recognized, it could be hypothesized that the leukemic transformation may have involved an oligopotent B/T lymphoid precursor. This case confirms the lineage heterogeneity of CML-BC and suggests that DNA analyses coupled to extensive immunophenotyping may allow further insight for a more precise recognition of both normal and leukemic ontogenesis.
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PMID:Hybrid lymphoid blast crisis of chronic myeloid leukemia with both immunoglobulin and T-cell receptor gene rearrangements. 196 Jan 35


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