Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An X;9;22 translocation was detected in bone marrow cells of a female patient with blastic crisis of CML. A dynamic study following 5-BrdU treatment showed that the inactive late-replicating X chromosome was the normal one. This pattern of X-chromosome replication appears to be superimposable on the most usual model found in congenital X/autosome translocations. It is suggested that preferential autosome translocation onto the active X chromosome could be the general rule in acquired X/autosome translocations associated with long survival.
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PMID:Inactive normal X in a female leukaemic patient with an acquired X/autosome translocation. 28 53

The chromosomes of a cell line (NALM-1) derived from the leukocytes of a patient with chronic myelocytic leukemia (CML) were examined with several banding techniques. The modal chromosome number was 46 and the cells contained a Philadelphia chromosome (Ph1), due to the standard translocation of the missing segment of the long arm of chromosome No. 22 onto the distal end of the long arm of chromosome No. 9, i.e., t(9;22) (q34;q11). The Ph1-positive modal cells of the NALM-1 line also had two common marker chromosomes, an extra X-chromosome, and missing chromosomes in groups No. 7, 9, and 15. Immunologic examination of the NALM-1 cells revealed them to have non-T-non-B (null) surface characteristics. An antigen specific for cells of acute leukemia and a human la-like antigen were detected. These facts suggested that the NALM-1 cell line originated from CML cells and maintained the cytogenetic and Immunologic characteristics of such cells.
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PMID:Cytogenetic study of a new Ph1-positive cell line (NALM-1). 30 41

Previous studies with the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) as a marker of cellular mosaicism demonstrated that polycythemia vera (PV) and essential thrombocythemia (ET) are clonal disorders of hematopoietic stem cells that can differentiate to erythrocytes, granulocytes, and platelets. To determine if the involved stem cells could also differentiate along the B-lymphoid pathway, we studied one woman with PV and one woman with ET. Of 117 Epstein-Barr virus-transformed B-lymphoblastoid lines expressing a single G6PD derived from the patient with PV, 108 expressed G6PD type A, the type characteristic of the abnormal clone. The ratio of 108:9 was significantly different from the one to one ratio predicted for this patient, which suggested that at least some circulating progenitors for B-lymphoid cell lines differentiate from the stem cell involved by the disease. Results obtained from the patient with ET were similar--104 of the 109 lymphoblastoid lines monotypic for G6PD expression displayed the enzyme type found in the abnormal clone of marrow cells. Therefore, in these patients, PV and ET, like chronic myelogenous leukemia, involve a stem cell pluripotent for the lymphoid as well as the myeloid series.
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PMID:Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia. 392 71

To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.
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PMID:Evidence for a multistep pathogenesis of chronic myelogenous leukemia. 697 38

Juvenile chronic myelogenous leukemia (JCML) is a myeloproliferative disease in which morbidity and mortality are primarily caused by nonhematopoietic organ failure from myelomonocytic infiltration or by failure of the normal bone marrow. Morphologic evidence of maturation arrest, karyotypic abnormalities, and progression to blast crisis are infrequent events. Viral infections and other reactive processes can initially mimic the clinical course of JCML, creating diagnostic problems. Because of the rarity of JCML and technical limitations, formal clonality studies have not been reported previously. Nine female JCML patients were identified by clinical criteria, characteristic 'spontaneous' in vitro cell growth, and negative cultures and titers for various viral agents. Peripheral blood and bone marrow samples were obtained at the time of diagnosis for cell separation and RNA and DNA isolation. To assess clonality, X-chromosome inactivation patterns were evaluated using three different, recently developed polymerase chain reaction-based clonality assays. All nine female JCML patients showed evidence for monoclonal origin of mononuclear cells at the time of diagnosis. Cell separation studies further traced the monoclonal origin back to at least the most primitive myeloid progenitor cell. Reversion to a polyclonal state was demonstrated after bone marrow transplant and also in one patient following treatment with 13-cis retinoic acid. This demonstration of clonality in JCML delineates it from the reactive processes and provides a basis for molecular genetic strategies to identify causally associated mutations.
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PMID:Clonality in juvenile chronic myelogenous leukemia. 780 95

Diagnosis of chronic myeloproliferative disorders (CMPD) can encounter difficulties due to overlaps and possible transitions between the different entities and their similarity to reactive myeloproliferations. In this study DNA analysis has been applied to improve differentiation of CMPD. All subtypes of CMPD analyzed, including chronic myeloid leukemia (CML), agnogenic myeloid metaplasia (AMM), polycythemia vera (PV), and essential thrombocythemia (ET), 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. Reactive myeloproliferations, by contrast, revealed a polyclonal inactivation pattern. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome (MDS) since the latter also exhibited clonal hematopoiesis. AMM belongs to the group of myeloproliferative syndromes. Up to now the cellular phase at onset of the disease (megakaryocytic myelosis) has not been analyzed for clonality of the hematopoietic cells. Granulocytes as well as bone marrow cells from the cellular phase and advanced stages of the disease revealed a monoclonal inactivation pattern of X-chromosomal genes. These results show that the cellular phase already represents a monoclonal, and hence probably a neoplastic, proliferation of a pluripotent stem cell. The monoclonality of granulocytes could also be demonstrated in patients with splenomegaly and strongly argues against a compensatory proliferation of regular hematopoiesis in this organ. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 244) for the detection of bcr-gene rearrangement. Despite possible morphological overlaps between different types of CMPD, bcr-gene rearrangement proved to be specific for CML and could be applied to differentiate CML from other CMPD in cases of uncertain morphological diagnosis. It is concluded that CMPD represent clonal hemopoietic disorders that probably have specific underlying genetic defects. Thus, DNA analysis can substantially aid in the differential diagnosis of CMPD.
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PMID:[Histopathology and molecular pathology of chronic myeloproliferative disorders]. 837 86

Idic(X)(q13) represents a rare but recurrent chromosomal abnormality in haematological malignancies. We present five new cases characterized by this particular aberration and review the literature on this subject. The patients were elderly females with a diagnosis of refractory anaemia (1/5), refractory anaemia with ringed sideroblasts (2/5), chronic myelomonocytic leukaemia (1/5), and Philadelphia chromosome-negative chronic myeloid leukaemia (1/5). Three out of the five patients demonstrated an increased proportion of bone marrow ringed sideroblasts. After a follow-up period of 30-57 months all patients but one are alive. Idic(X)(q13) always occurred as the sole chromosomal abnormality, either in one or in two copies. We confirmed the dicentric nature of the aberration by fluorescence in situ hybridization (FISH) on metaphases as well as interphase nuclei using an X-chromosome-specific alpha-satellite probe, and performed chromosome painting to visualize possible additional chromosomal changes involving the X chromosomes. Our findings and the data of 17 previously published cases indicate that idic(X)(q13): (1) may play a significant pathogenetic role in haematological malignancies affecting exclusively females and deriving predominantly from early progenitor cells; (2) is frequently associated with a pathological iron accumulation; (3) indicates a variable prognosis.
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PMID:Isodicentric (X)(q13) in haematological malignancies: presentation of five new cases, application of fluorescence in situ hybridization (FISH) and review of the literature. 854 34

To clarify the extent of cell lineage involvement in chronic myelogenous leukemia (CML), we investigated the bcr gene rearrangement and clonality using the X-chromosome-linked restriction fragment length polymorphism (RFLP) methylation method in T lymphocytes and granulocytes. We examined the granulocyte and T-cell fractions from the peripheral blood of seven female patients with CML during the chronic phase; patients were heterozygous for RFLPs at the phosphoglycerate kinase (PGK) or the hypoxanthine phosphoribosyltransferase (HPRT) gene. RFLP-methylation analysis of granulocytes demonstrated a monoclonal pattern in six of the seven patients and a rearranged bcr gene in all seven patients. In contrast, T lymphocytes exhibited a polyclonal pattern in six cases; in one case, a faint band was observed following methyl-sensitive enzyme cleavage. The bcr gene analysis in T lymphocytes showed the germline in every case. Our results indicate that the majority of T lymphocytes are polyclonal during the chronic phase of CML and confirm previous reports based on glucose-6-phosphate dehydrogenase, cytogenetic, and bcr rearrangement analyses.
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PMID:The majority of T lymphocytes are polyclonal during the chronic phase of chronic myelogenous leukemia. 859 8

Megakaryocyte proliferation in bone marrow is a feature common to the three Philadelphia negative chromosome myeloproliferative disorders (MPD)--essential thrombocythemia (ET), polycythemia vera, and myelofibrosis with splenic myeloid metaplasia--and chronic myelocytic leukemia. Enlarged megakaryocytes, clustering in close neighbouring with multilobulated nuclei are the hallmark of all the Philadelphia negative chromosome MPD. Clonality of hematopoietic cells, based on X-chromosome inactivation can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. A significant increase in circulating CFU-MK has been repeatedly observed in MPD as well as a spontaneous megakaryocyte colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation with a functional defect of the TPO-MPL pathway may play a major role in spontaneous megakaryocyte growth. There is presently no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However the role of platelets activation in the pathogenesis of ischemic erythromelalgia has been established.
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PMID:[Dysmegakaryocytopoiesis and dysthrombopoiesis in myeloproliferative syndromes]. 907 18

In November 1996, word reached the University of Washington that Philip Fialkow and his wife, Helen, had died while trekking in Nepal. Over a 30-year period, Dr Fialkow and his colleagues used the cellular mosaicism resulting from X-chromosome inactivation in females as a marker system to investigate the clonal development of human hematopoietic disorders. This review discusses the impact that these studies have had on our understanding of hematopoietic stem cell relationships and the pathogenesis of human neoplasia in general. To appreciate the special role played by studies on clonality, it is necessary to consider how little was known about the origin of leukemias and myeloproliferative disorders and the limited techniques available for their study in the early to mid 1960s. Dr Fialkow and his coworkers were the first to show that myeloproliferative disorders and acute myelogenous leukemias (AML) are clonal diseases at the time of diagnosis and to elucidate the level of differentiation manifested by the originating cell type. Although the myelodysplastic disorders were found to involve a pluripotent stem cell, heterogeneity was found in the level of stem cell involvement in AML. Evidence was obtained to support a multistep pathogenesis of these diseases as well as a clonal but cytogenetically normal stage in some cases of Ph-positive chronic myelogenous leukemia, AML, acute lymphoblastic leukemia and myelodysplasia.
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PMID:Clonal development of myeloproliferative disorders: clues to hematopoietic differentiation and multistep pathogenesis of cancer. 951 69


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