Jurgen Thiele

..6% and 32.3 %. In conclusion, a more accurate classification of ET is warranted by regarding the WHO criteria that include histopathology as a major feature for diagnosis...

..Therefore, so-called masked PV in patients with ET or simultaneous PVR-1 gene expression and endogeneous erythroid colony growth in ET patients are probably in keeping with initial PV mimicking ET...

..To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term STI571 therapy...

..In conclusion, certain sets of morphological parameters allow a distinction between autonomous and reactive polycythemias and therefore enhance significantly diagnostic validity...

..In conclusion, PV is characterized by a distinctive pattern of histopathology that has been gained in an independent and blind fashion and therefore, dissolves arguments about failing specificity...

..Data on proliferative activity and apoptosis in general supported in vitro findings concerning the inhibitory effect of this agent on growth associated with a tendency for stimulated apoptosis, at least in responding patients...

..Because cytogenetic response and reduction of micromegakaryocytes seem to be linked, this feature may be useful to monitor therapeutic efficacy by evaluating BM morphology...

..A sprouting of vascular structures into the donor heart after orthotopic cardiac transplantation has to be assumed, as does a pivotal role of the mesenchymal stem cells of the BM in the development of mCh...

..Because cytogenetic response and reduction of atypical micromegakaryocytes are linked, this feature may be useful to monitor therapeutic efficacy...

..In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy...

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..In CIMF progressive myelofibrosis occurred in more than 50% of patients according to the last biopsy specimen; however, this figure increased according to relevant clinical data in the follow-up period...

..Regarding these results, a schematic procedure is proposed to be used for daily routine diagnosis concerning the discrimination of MPDs...

..Development of myelofibrosis in IMF is obviously due to disease progression unrelated to stage at diagnosis and not significantly influenced by treatment modalities...

..This phenomenon is more extensively expressed than previously expected and may be related to an enforced repair of the damaged myocardium during the post-transplant period as the sequel of myeloablative (cardiotoxic) conditioning...

..To analyse systematically therapy-induced lesions of haematopoiesis in chronic idiopathic myelofibrosis (IMF)...

..Contrasting the wealth of clinical data, bone marrow (BM) changes during therapy have been relatively rarely studied; information is particularly lacking regarding specific features of megakaryocytopoiesis...

..Comparison of clinical and survival data of the Vienna cohort with the historical Cologne series revealed an overall congruence. This study highlights the impact of BM morphology for the differentiation between true vs false ET...

..Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover...

..This putative pathomechanism is significantly associated with the evolution of MMM...

..As with PMF, morphology plays a distinctive role in diagnosis, particularly for its differentiation from early-stage PV or prodromal PMF associated with thrombocytosis...

..Finally, an increase in dysplastic changes and immaturity of cell lineages signals a transition into blastic crisis...

..Myelofibrosis (MF) implies an increase in the bone marrow (BM) fiber content without referring to quantity or quality (reticulin vs. collagen)...

..The non-transplantable stromal compartment includes the vascular endothelium with a predominance of recipient cells. The minimal mCh of this population implies probably a donor-derived origin (endothelial progenitor cells)...

..In conclusion, more elaborate evaluations including standardized grading of MF is warranted by regarding bone marrow biopsy specimens in association with clinical parameters including follow-up examinations...

..On the other hand, in follow-up examinations of BM specimens, ANA failed to show a stimulation of myelofibrosis in ET, provided diagnosis was established according to the World Health Organization criteria...

..In conclusion, BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies...

..A scrutinized discrimination of thrombocythemias resulting in a clear-cut diagnosis of true versus false ET is warranted by a professional evaluation of BM biopsies in ongoing and prospective clinical trials...

..In conclusion, trisomy 8 has been demonstrated already in the prodromal stages of CIMF and therefore is not limited to classical fibro-osteosclerotic manifestations...

..In conclusion, the dynamics of the disease process in CIMF are characterized by evolving MF in the BM and closely associated changes of relevant hematological findings...

..A comparison of clinical data and BM morphology reveals that biomarkers (EPO, EECs, PRV-1, JAK2) show an overlapping pattern of positivity between the different subtypes of MPDs...

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..Regarding prognosis, early CIMF is associated with a significantly more favorable survival than advanced stages...

..However, contrasting ANA, HU generated defects of differentiation consistent with significant dysplastic changes. In conclusion, concern about a possible leukemogenic capacity following long-term HU therapy is supported by our findings...

..The consensus for measuring myelofibrosis by clear and reproducible guidelines achieved by our group should allow for precise grading during the disease process and after therapy...

..In conclusion, persuasive evidence has been produced that myelofibrosis in IMF is characterized by a stepwise progression and that this process is not significantly influenced by current treatment strategies...

..A striking conversion of MCh to a recipient cell type was found in leukemic relapse with a more than 90% host-derived erythroid and megakaryocytic cell population in 4 patients approximately 643 days after BMT...

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..e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia...

..In addition, patients showing a rapid progression of myelofibrosis during IFN and HU treatment of Ph1+-CML are generally associated with a poor risk outcome and a significant worsening of survival...

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..In conclusion, morphological and clinical parameters have been validated by this study, which are consistent with a set of diagnostic criteria to recognize initial or prefibrotic precursor stages of IMF...

..Only in a small proportion not a failing methodology, but initial stages of the disease process requires sequential examinations to reach a correct diagnosis...

..Moreover, quantity of erythropoiesis and amount of reticulin fibers (myelofibrosis) exerted a significant impact on engraftment status...

..In this context the updated diagnostic criteria of the Polycythemia Vera Study Group (PVSG) are generally accepted, although histopathologic features of the bone marrow were only marginally considered...

..However, little information exists on whether these groups represent stable categories of the different classification systems and whether therapeutic regimes exert any influence on the putative shift of histological patterns...

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..Opposed to a repeatedly discussed pathomechanism, we failed to demonstrate any quantitative relationships between the extent of lymphocyte proliferations and occurrence or progression of myelofibrosis...

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..This feature was assumed to contribute to a maintenance of steady-state hematopoiesis expressed by a nonaltered bone marrow cellularity in our specimens...

..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...

..Furthermore, it may even warrant follow-up studies and repeated bone marrow examinations in initially unclassifiable cases...

..The latter feature may be triggered by increased degradation of senescent megakaryocytes, frequently occurring as endstages of growth factors-releasing fibrogenetic megakaryopoiesis...

..For this reason, it should be mandatory to enter morphological criteria into prospective clinical trials on CML, not only for diagnostic purpose, but also for a proper evaluation of different survival patterns...

..For this reason, a presumptive defect in the recovery of normal and clonally transformed stem cells is speculated to add to the worsening of prognosis by causing the well-known bone marrow insufficiency in terminal stage PV and IMF...

..Discrimination between these entities is warranted, because of a significant difference in presenting haematological data, follow-up and life expectancy...

..However, further investigations are necessary to identify, isolate and enrich the cardiomyocytic stem cells more specifically for future curative therapeutic options in patients with severe ischemic cardiomyopathy...

..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%)...

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..Moreover, characterization of early stage IMF probably exerts an impact on survival and may influence the decision to perform a BM transplantation...

..Finally, no significant influence of Agrylin((R)) on the evolution of myelofibrosis is detectable and there is a general improvement of hematological data especially in cIMF...

..Although CD34 progenitors play a crucial role during bone marrow transplantation (BMT), there is only scant knowledge concerning their lineage-restricted mixed chimerism (MCh)...

..These findings point towards a CD34+ progenitor cell origin of the (leukemic) endothelial cell layer and suggests that their dysfunction may contribute to an expansion of the neoplastic clone...

..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...

..According to our findings these patients should be classified as having either ET, CIMF or MDS and show a significantly different survival pattern...

..We tried to elucidate the coexpression of both molecules in colorectal cancer to demonstrate possible correlations with clinical, pathological, and prognostic data...

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..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...

..The revised WHO classification incorporates hematological, morphological, and molecular-genetic parameters to generate a consensus-based working diagnosis...

..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...

..In conclusion, our data support the anti-angiogenic capacity of imatinib by normalization of vascularity. In contrast, hematologic response following IFN treatment is independent from BM angiogenesis...

..It has been shown that examination of bone marrow specimens enhances the diagnostic reliability and also enables the recognition of evolving myelofibrotic transformation in MPDs...

..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...

..Our studies identify a new regulatory region in the KIT molecule and strongly suggest that patients with extracellular KIT mutations respond to tyrosine kinase inhibitors...

..We sought to quantitatively and objectively evaluate histomorphologic tumor regression and establish a relevant prognostic regression classification system for esophageal cancer patients receiving neoadjuvant radiochemotherapy...

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..According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype...

..Although novel genetic and molecular approaches have significantly improved the way we classify Ph- MPD, a combined clinicopathologic approach, including representative bone marrow specimens, still remains the yardstick for diagnosis...

..An altered rate of apoptosis and cell cycling may contribute to accumulation of mast cells in mastocytosis...

..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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..Bone marrow histologic and hematologic remissions characterize CR and CR/PR, respectively. The panel agreed that the CI response category is applicable only to patients with moderate to severe cytopenia or splenomegaly...