Quantifying chimeric cardiomyocytes.
Explore the source record for details and available documents.
Cell Count↗
Biomedical subjects
Juergen Thiele
Publications and source records attributed to Juergen Thiele.
Expression of Bcl-2 and Bcl-xL in cutaneous and bone marrow lesions of mastocytosis.
Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues. To investigate whether an altered regulation of mast cell apoptosis might be involved in the pathogenesis of mastocytosis, expression of the apoptosis-preventing molecules bcl-2 and bcl-xL was studied by immunohistochemistry in skin and bone marrow lesions of mastocytosis patients. In addition, reverse transcription-polymerase chain reaction was used to investigate levels of bcl-2 and bcl-xL mRNA in cutaneous mastocytosis lesions. Since activating mutations of c-kit are known to be associated with some forms of mastocytosis, human mast cell cultures were also stimulated via c-kit and the expression of bcl-2 and bcl-xL was assessed by immunoblotting. In patients with mastocytosis, the expression of bcl-2 protein but not bcl-xL in cutaneous mast cells was significantly enhanced, compared to healthy controls. Evaluating different subgroups of adult and pediatric mastocytosis patients, all groups were found to express significantly increased levels of bcl-2 protein, and none of the patient groups was found to overexpress bcl-xL, with the exception of solitary mastocytomas that showed a tendency for up-regulated bcl-xL protein. Furthermore, the expression of bcl-2 mRNA was significantly enhanced in cutaneous lesions of adult and pediatric patients, while bcl-xL mRNA levels were only slightly increased in pediatric, but not in adult patients with mastocytosis. In contrast to the skin lesions, bone marrow infiltrates of patients with systemic mastocytosis showed only low or absent immunoreactivity for bcl-2, but marked expression of bcl-xL. In vitro, stimulation of two different mast cell culture systems by activation of c-kit resulted in up-regulation of bcl-2 and also in an increase of bcl-xL, although less pronounced. Thus, overexpression of bcl-2 and bcl-xL leading to prolonged survival of mast cells may contribute to the pathogenesis of mastocytosis. Our findings may help to develop new strategies for the treatment of this disease.
Adult↗
Bone marrow manifestation of Lyme disease (Lyme Borreliosis).
Explore the source record for details and available documents.
Adult↗
Mixed chimerism of bone marrow vessels (endothelial cells, myofibroblasts) following allogeneic transplantation for chronic myelogenous leukemia.
Experimental findings support the hypothesis that within the functional network of the bone marrow (BM) microenvironment the endothelial cells (ECs) exert a pivotal role as gatekeepers by controlling the trafficking and homing of progenitor cells. However, little information is available concerning the origin of ECs after allogeneic bone marrow transplantation (BMT) in CML. To determine the extent of mixed chimerism (MCh) a simultaneous immunohistochemical and fluorescence in-situ hybridization (FISH) study was performed on BM biopsies derived from patients following sex-mismatched BMT with full unmanipulated BM. ECs were identified by their staining with CD34 and the myofibroblasts (MFs) of large vessels were labeled by an antibody against alpha-smooth muscle actin. For sex-typing and demonstration of the bcr/abl fusion product appropriate commercially available probes and detection systems were applied. Contrasting a total congruence of labeling in control samples five patients showed donor type ECs in the early posttransplant period in about 20%. In the remaining four patients the amount of donor type ECs increased slightly after the third month up to 30%. A total of 26 MFs could be identified lining large capillaries and arterioles that exclusively revealed a host origin. Following successful engraftment only very few of the persistent host-derived ECs also displayed the bcr/abl gene. In five patients, a conversion of MCh from donor to host type ECs was recognizable during the evolution of leukemic relapse. This finding was accompanied by a bcr/abl rearrangement of about 10% of these cells. In conclusion, following myelo-ablative therapy, a survival of a considerable number of ECs and MFs of the vessel walls has been found implying persistence of host-derived vascular structures of the BM stroma. However, in only a small proportion bcr/abl+ ECs and thus minimal residual disease was detectable. Evolution of leukemic relapse was characterized by conversion of MCh with almost total loss of donor type ECs and increase in number of bcr/abl+ ECs.
Adult↗
Impact of bone marrow morphology on multivariate risk classification in chronic myelogenous leukemia.
Explore the source record for details and available documents.
Bone Marrow↗
Mixed chimerism of bone marrow CD34+ progenitor cells (genotyping, bcr/abl analysis) after allogeneic transplantation for chronic myelogenous leukemia.
BACKGROUND: Although CD34 progenitors play a crucial role during bone marrow transplantation (BMT), there is only scant knowledge concerning their lineage-restricted mixed chimerism (MCh). METHODS: An immunohistochemical and fluorescence in situ hybridization study was performed on bone marrow biopsies derived from 11 patients with chronic myelogenous leukemia after sex-mismatched BMT to quantify the CD34 cell population and their expression. After proper identification by a lineage-specific monoclonal antibody, X chromosome- and Y chromosome-specific probes were used for sex typing and for labeling of the locus commercially available detection systems were applied. RESULTS: After successful engraftment, 241 progenitor cells were identified at days 9 to 586 of the posttransplant period. Overall incidence of MCh was 24% with a tendency to decline after day 100 to 15%. The gene was detectable in only 10% of these precursors and decreased to less than 4% after more than 6 months. Approximately 0.5 to 5.5 years after BMT in six patients, a manifest leukemic relapse occurred, which was accompanied by a conversion of donor-to-host-type progenitors. This phenomenon involved up to 94% of the 303 evaluable CD34 cells and also included a retrieval of the translocation gene in approximately 50% of this population. CONCLUSION: The lineage-restricted MCh of progenitors after BMT is in keeping with the assumption that leukemic (bcr/abl ) precursors represent only a fraction of the total host-derived (chimeric) CD34 cells. These residual clonally transformed progenitors survive myeloablative treatment and thus may be the source for a later relapse.
Adult↗
Mixed chimerism of the resident macrophage population after allogeneic bone marrow transplantation for chronic myeloid leukemia.
BACKGROUND: Bone marrow macrophages have been recognized to play a crucial role in the functional network that constitutes the microenvironment. In chronic myelogenous leukemia (CML), neoplastic macrophages are presumably responsible for the expansion of the leukemic cell clone. So far, no information is available about a persistence of host-type macrophages after allogeneic bone marrow transplantation (BMT) implicating a lineage-specific mixed chimerism. METHODS: Bone marrow trephine biopsies were investigated in eight male and five female patients with CML after BMT after a sex-mismatched host/donor constellation. Techniques included immunophenotyping (CD68) for identification of resident macrophages and a simultaneous genotyping with X- and Y-chromosome-specific DNA-probes (fluorescence in situ hybridization). Normal bone marrow and specimens of CML patients before BMT served as controls. RESULTS: Contrasting an almost 100% congruence with the genotyping in the controls, a mixed chimerism of the CD68+ macrophages and the other host myeloid cells was found. Until 3 months after BMT, incidence of host-type macrophages ranged from 8% to 10%. This feature was also identifiable in the peculiar subset of pseudo-Gaucher cells (PGCs). The number of host-type macrophages failed to decline significantly during the early posttransplant period, because after almost 4 months these were still detectable. On the other hand, in patients showing an initial-to-manifest leukemic relapse, an insidious conversion of up to 50% from the donor to host-type macrophages and myeloid cells occurred. CONCLUSIONS: The CD68+ resident bone marrow macrophage population including PGCs are involved in the lineage-specific chimerism and minimal residual disease after BMT in CML.
Biopsy, Needle↗
Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients.
Diagnosis of essential thrombocythemia (ET) has been usually established by regarding the criteria of the Polycythemia Vera Study Group. Accordingly, a retrospective clinicopathological study was performed on 120 patients with a follow-up ranging between 5 and 13 years and repeated bone marrow trephine examinations. Following the new WHO classification, at presentation patients revealed three distinctive patterns of bone marrow (BM) features: (true) ET in 43 patients, prefibrotic idiopathic myelofibrosis (IMF) in 50 patients, and early IMF in 27 patients. Heterogeneity of morphological features was associated with correspondingly expressed laboratory data. Contrasting initial and early IMF, patients with true ET displayed an about 80% probability to lack splenomegaly, anemia, and increase in the LDH and LAP values and also failed to show any myeloblasts or erythroblasts on the peripheral blood films. Follow-up examinations including sequential BM biopsies (mean interval 39 +/- 31 months) disclosed that of the 43 patients with true ET only one developed an increase in reticulin. On the other hand, 65 of 77 patients with prefibrotic and early IMF evolved into overt myelofibrosis-osteosclerosis. Moreover, survival analysis demonstrated significant differences in our patients. A neglectable proportion of life loss according to a sex- and age-matched general population was found in true ET (less than 11%) opposed to IMF without or mild fibrosis (range 21% to 32%).
Adult↗
Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma.
BACKGROUND: MUC5AC represents a mucin peptide core expressed in normal gastric epithelia. Its presence in gastric carcinomas was previously described as a characteristic of gastric differentiation. METHODS: MUC5AC reactivity was investigated by immunohistochemistry and correlated with clinicopathological variables in a large series (n = 200) of gastric carcinomas. RESULTS: A statistically significant association between MUC5AC positivity and parameters of cancer progression (pTNM staging and grading) could not be observed. However, MUC5AC exhibited correlations with certain subtypes of histopathological differentiation. A significant reduction of MUC5AC expression was evident in mucinous and undifferentiated carcinomas according to the World Health Organization classification, as well as in type III cancers according to the Goseki classification system. Furthermore, reduced MUC5AC reactivity (confined to up to 35% of the tumor area) was significantly correlated with an unfavorable prognosis of all patients in univariate and multivariate analysis. The same association could be observed in the subgroup of pTNM stage I patients (n = 60). CONCLUSIONS: A significant reduction of gastric differentiation as reflected by MUC5AC immunoreactivity represents a marker of worse survival probability in gastric cancer. Finally, reduced MUC5AC positivity defines a high-risk subgroup of pTNM stage I patients.
Adult↗
Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia).
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.
Bone Marrow↗
Dynamics of CD34+ progenitor cells following allogeneic bone marrow transplantation in Ph1+CML--an immunohistochemical study on 113 patients with sequential trephine biopsies.
A retrospective immunohistological and morphometric study was performed on bone marrow trephine biopsies derived from 113 patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph(1+)-CML) before and at standardized intervals following allogeneic transplantation (BMT) with full unmanipulated marrow specimens. The purpose of this investigation was to quantify CD34+ progenitor cells and to determine their dynamics during the post-transplant period. Moreover, we tried to correlate their number with corresponding changes in the amount of nucleated erythroid precursors and megakaryocytes including pro- and megakaryoblasts and the fiber content. Monitoring the quantity of precursors after BMT revealed a very rapid recovery in comparison to a control group. However, a more detailed evaluation showed that at day 22 +/- 6 a higher number of progenitor cells was significantly associated with an earlier independence for platelet transfusion and also with a more pronounced growth of erythro- and megakaryopoiesis including their precursor cells. Furthermore, a slight increase in the density of the fibrous matrix (reticulin fibers) was present in these patients that were characterized by a more favorable engraftment. The latter feature sheds some light on the complex pathomechanisms of homing and differentiation of progenitors. In confirmation with in vitro findings, this phenomenon is dependent on proper anchoring sites to the fibrous bone marrow stroma. Finally, the size of a full BM graft exerted a distinctive influence on the number of CD34+ precursors in the early post-transplant period. In conclusion, the present study has validated a number of BM features by focusing on the CD34+ progenitor cells and associated hematopoietic reconstitution including reticulin fibers and precursor cells of the erythroid and megakaryocyte lineage, which are not readily evaluable by fluorescence-activated cell sorting (FACS) analysis.
Adolescent↗
Essential thrombocythemia with ringed sideroblasts: a heterogeneous spectrum of diseases, but not a distinct entity.
BACKGROUND AND OBJECTIVES: According to the recently published WHO-classification essential thrombocythemia with ringed sideroblasts (ET/RS) remains an ambiguous category which may be considered as myelodysplastic/myeloproliferative disease, unclassifiable. Because until now only case reports or very small series of patients have been described, a more systematically performed study is warranted. DESIGN AND METHODS: A retrospective evaluation was carried out on 38 patients with the diagnosis of ET/RS and more than 15 % ringed sideroblasts on smears. Simultaneously performed bone marrow biopsies, follow-up examinations and survival data were also available. RESULTS: Based on cytological features and particular bone marrow findings including immunohistochemistry three patterns could be determined. These were associated with different clinical features and in particular prognosis. Group I included six patients whose diagnosis was consistent with ET, group II comprised 21 patients revealing prefibrotic and early fibrotic chronic idiopathic myelofibrosis (CIMF) and finally 11 patients (group III) displayed myelodysplastic syndromes (MDS). Follow-up studies revealed that no patient with ET showed a fiber increase but eight CIMF patients developed overt myelofibrosis and four patients of the MDS group developed secondary acute myeloid leukemia. In comparison with a control group of 39 patients with true ET, prognosis was significantly different because our cohort showed a median survival of 100 months that contrasted significantly with the 170 months in the patients with true ET. INTERPRETATION AND CONCLUSIONS: Ringed sideroblasts are not a pathognomonic feature of MDS, but may indicate a dysplasia probably associated with a primary or secondary disturbance of iron metabolism in a variety of disorders. For this reason, a more accurate classification of so-called ET/RS patients is warranted by evaluation of smears and in particular bone marrow biopsy specimens. According to our findings these patients should be classified as having either ET, CIMF or MDS and show a significantly different survival pattern.
Aged↗