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

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.
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PMID:Immunophenotypic characterization of human bone marrow endosteal cells. 1039 6

Differentiation of an elevated, repeatedly determined platelet count (> or =500x10(9)/l) includes the discrimination between reactive causes generated by a variety of underlying conditions and a neoplastic myeloproliferative disorder (CMPD). In addition to clinical findings, the evolution of laboratory data during follow-up and histology of the bone marrow exerts a significant diagnostic impact. Characteristic features are not only expressed by hematopoiesis, but also by the myeloid stromal compartment. While the megakaryocyte-rich subtype of chronic myeloid leukemia (CML) and the 5q(-) syndrome (MDS) are dominated by abnormal micromegakaryocytes, in polycythemia vera (PV) this cell lineage reveals a pleomorphous appearance. In essential thrombocythemia (ET), a prevalence of giant megakaryocytes with deeply lobulated (staghorn-like) nuclei may be encountered. A clear-cut discrimination of ET from early (hypercellular) stages of idiopathic (primary) myelofibrosis (IMF) presenting with thrombocythemia becomes possible, provided the conspicuous atypical features of megakaryopoiesis characterizing the latter entity are taken into account. Moreover, CML displays a predominance of the granulocytic lineage whereas PV shows a panmyelosis or trilineage proliferation, involving erythropoiesis, in particular. In contrast, erythropoiesis is markedly reduced in CML and to a lesser degree also in IMF. In CMPDs extreme values of iron deposits may be found, ranging from a total lack (PV) to minor amounts (CML) and a normal staining reaction (ET). Similar results are exhibited regarding reticulin fibrosis, which is usually not present in ET, rarely observed in PV and detectable to a variable degree in CML and IMF.
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PMID:[Thrombocytosis versus thrombocythemia--differential diagnosis of elevated platelet count]. 1066 67

Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow. Therefore, dynamics of hematopoiesis is mainly defined by these two parameters. However, since only few data are available from previous studies, we performed a retrospective analysis to elucidate some aspects of this complex pathomechanism. A total of 400 patients with chronic myeloproliferative disorders (CMPDs) and corresponding reactive bone marrow lesions were enrolled into this study. Apoptosis was detected in bone marrow tissue by the ISEL-technique and topoisomerase II alpha expression was demonstrated by the monoclonal antibody Ki-S1. Furthermore, by determination of the proliferating-cell nuclear antigen labeling (PCNA) index, we were able to calculate the proportion of cells in the G2/M phase, because both nuclear antigens are expressed in different phases of the cell cycle. Patients with IMF, PV, and ET revealed a normal range of apoptosis, whereas in chronic myeloid leukemia (CML) a significant increase could be observed. On the other hand, IMF and PV were characterized by a raised proliferative activity. Dynamics of hematopoiesis was assessed by calculation of the so called hematopoietic turnover index. In CML and reactive lesions no alterations of this parameter were detectable, but IMF and PV showed a significant increase. Survival analysis disclosed a relevant worsening of life expectancy for patients with reduced apoptosis and proliferation. In conclusion, our in-situ results confirm and extend previous experimental data on hematopoietic cell kinetics. In this context, a greater regenerative capacity of hematopoiesis may be reflected by an increased rate of apoptosis and/or proliferation and therefore is associated with a more favorable outcome.
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PMID:[Apoptosis and proliferation in the bone marrow of chronic myeloproliferative disorders--biological and prognostic importance]. 1066 69

The broad spectrum of clinical and hematological as well as histomorphological findings at diagnosis of chronic myeloproliferative disorders (CMPDs) is significantly associated with prognosis. However, in this context the impact of bone marrow histology is still being controversially discussed. This feature applies to CML in particular. Therefore, risk classification is mainly based on clinical data. In order to evaluate the predictive value of bone marrow morphology we performed a retrospective study on a total of 1023 patients with CMPDs. Relative survival rates and a disease-specific loss of life expectancy were calculated to adjust the age- and gender-specific mortality in older patients. Patients with chronic myeloid leukemia (CML) showed an average life expectancy of 5 years, with significantly longer survival times under interferon treatment. In contrast, the ET group did not disclose any relevant reduction in life expectancy. Initial bone marrow fibrosis and a reduction in erythropoiesis were the most important prognostic features in CML. Furthermore, Pseudo-Gaucher cells indicated a favorable outcome in the cohort of patients receiving chemotherapy. On the other hand, peripheral myelo- and erythroblasts were correlated with a worsening in survival. Regarding IMF, a simplified multivariate risk score was constructed, including age, hemoglobin level, platelet and leukocyte counts, and a leuko-erythroblastic blood picture as most important variables. The three risk groups derived showed significantly different survival patterns, but in this calculation bone marrow histology exerted no major influence on survival. On the other hand, initial (prefibrotic) stages of IMF revealed a better prognosis. In conclusion, our results underline the importance of bone marrow morphology in CMPDs, since significant correlations with patients' outcome were calculated. Particularly in CML, myelofibrosis and reduction of erythropoiesis were associated with survival and, thus, must be regarded as important predictive and independent parameters.
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PMID:[Prognostic factors and survival in chronic myeloproliferative disorders]. 1066 70

A set of clinical and pathological criteria for the diagnosis and staging of Philadelphia chromosome-negative myeloproliferative disorders (Ph(1-)-MPDs) is presented by including bone marrow histopathology as a significant tool to identify the early, manifest, and advanced stages of essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis/agnogenic myeloid metaplasia (IMF/AMM). This combined approach provides a pathognomonic clue to each of the different subtypes of Ph(1-)-MPDs and further enables recognition of the various steps in the evolution of the myeloproliferative process Increase and clustering of giant to large megakaryocytes with mature cytoplasm and multilobulated staghorn-like nuclei in a normal or only slightly increased cellular bone marrow represent major hallmarks of ET. Loose assemblies of small to giant pleiomorphic megakaryocytes containing deeply lobulated nuclei together with a proliferation of erythro- and granulopoiesis (panmyelosis) are the specific lesions of PV. The initial prefibrotic and the overt and more advanced myelofibrotic stages of IMF/AMM show a pronounced proliferation of an abnormal megakaryo- and granulopoiesis dominated by clustered atypical medium-sized to giant megakaryocytes with cloud-like, bulbous, and often hyperchromatic nuclei, which are not seen in allied subtypes of MPDs including chronic myeloid leukemia (Ph(1+)-CML) and myelodysplastic syndromes (MDS). The presented clinical and pathological criteria modify the Polycythemia Vera Study Group (PVSG) proposals for the Ph(1-)-MPDs by including bone marrow histopathology and are in keeping with features outlined in the new World Health Organization classification. The latter allows the differentiation of true ET from reactive thrombocytosis and from thrombocythemias as an eventually presenting finding in PV, IMF/AMM, MDS, and Ph(1+)-CML. Moreover, these diagnostic guidelines are able to separate latent and early PV from secondary erythrocytosis and to detect the prefibrotic and early stages of IMF/AMM. Myelofibrosis is not a feature of ET and is rarely observed in PV at time of diagnosis, but it becomes apparent during long-term follow-up and constitutes a prominent lesion during the course of IMF/ AMM. Life expectancy is almost normal in ET and is also not significantly altered during the first, but compromised during the second, decade of follow-up in PV. On the other hand, survival is substantially shortened in IMF/AMM, even for patients with thrombocythemia as a frequent finding of prefibrotic and early stage IMF/AMM.
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PMID:Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). 1221 11

To investigate the relationship between socs3 mRNA expression and jak2v617f point mutation in bcr-abl negative patients with myelo-proliferative disease (MPD), 62 bcr-abl negative MPD patients (26 cases of PV, 26 cases of ET, 9 cases of IMF, and one case of CNL) were arranged as experiment group, and the others (20 cases of CML, 10 cases of AL and 15 healthy volunteers) were arranged as control group. All the diagnosis had been made according to the 2001 WHO criteria. jak2v617f point mutation was detected by AS-PCR and confirmed by direct sequencing. The expression level of socs3 mRNA was measured by RT-PCR. The association jak2v617f point mutation with socs3 mRNA expression in bcr-abl negative MPD patients was observed and analyzed. The results showed that among 62 bcr-abl negative MPD patients, the somatic jak2v617f point mutation was positive in 44 patients (PV 23, ET 15, IMF 5, CNL 1) while negative in the other 18 patients and control group. The expression of socs3 mRNA could be detected in 39 patients from 44 jak2v617f mutation positive patients and in 10 patients from 18 jak2v617f mutation-negative patients. There was a statistically significant difference in socs3 mRNA expression rates between jak2v617f mutation positive and negative group (chi(2) = 8.44, p < 0.005). There was a statistically significant difference in socs3 mRNA expression levels between jak2v617f mutation positive and negative groups (p = 0.035). It is concluded that there is a statistically significant difference in the expression level of socs3 mRNA in the patients between jak2v617f mutation positive group and negative group.
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PMID:[Relationship between socs3 mRNA expression and jak2v617f point mutation in bcr-abl negative patients with myelo-proliferative disease]. 1854 12