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)

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.
 ...
PMID:[Prognostic factors and survival in chronic myeloproliferative disorders]. 1066 70

A clinicopathological study was conducted on 351 bone marrow trephine biopsies derived from 124 patients with chronic myeloid leukemia (CML) at standardized endpoints before and after allogeneic bone marrow transplantation (BMT). The purpose was to investigate quantitative changes of the nucleated erythroid precursor cell population and other associated features such as resident bone marrow macrophages and myelofibrosis and to elucidate their relevance on engraftment parameters. Monoclonal antibodies were applied for the identification of erythroid precursors and the labeling of mature macrophages; argyrophilic (reticulin-collagen) fibers were demonstrated by a silver impregnation technique. Following morphometric analysis of the pregraft bone marrow specimens statistical evaluation was in line with an adverse correlation between early to moderate reticulin fibrosis and amount of erythropoiesis. Moreover, a significant relationship was calculable between numbers of erythroid precursors and CD68+ macrophages. After myelo-ablative therapy and BMT a pronounced decrease in cellularity and in the quantity of erythropoiesis was found. Comparable with the pregraft samples, a significant association between erythroid precursors and macrophages could be determined in the regenerating donor bone marrow. A pretransplant relevant reduction of the red cell lineage and a manifest (reticulin) myelofibrosis indicating an advanced stage of disease were accompanied by a significant delay to reach transfusion independence. This result was further supported by comparable findings in trephine biopsies performed in the early post-transplant period (second month after BMT). Corresponding examinations revealed an enhancement of fiber density and a decrease in erythropoiesis in those patients who did not conform with the usually accepted criteria for successful engraftment. In conclusion, compelling evidence has been produced that a significantly reduced amount of erythroid precursors, which is usually associated with myelofibrosis in the pretransplant bone marrow, exerts an impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial and numerical relationship between the erythroid lineage and resident (mature) macrophages is observable, in particular in the state of regeneration after BMT.
 ...
PMID:Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow specimens of CML patients following allogeneic transplantation. 1094 32

A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express alpha-D-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40-50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9-45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.
 ...
PMID:Macrophages and their subpopulations following allogenic bone marrow transplantation for chronic myeloid leukaemia. 1099 76

Following myelo-ablative treatment and allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) histopathological features assumed to exert a significant impact on engraftment have been rarely investigated systematically. This review is focused on immunohistochemical and morphometric techniques involving nucleated erythroid precursors, resident macrophages and their various subsets, megakaryocytes and finally argyrophilic (reticulin-collagen) fibers. Regarding standardized intervals of examination in the postgraft sequential trephine biopsies a pronounced reduction in cellularity was obvious and accompanied by a decrease in the quantity of erythro- and megakaryopoiesis. A significant correlation between the number of erythroid precursors and CD68+-macrophages could be determined in the areas of regenerating hematopoiesis. This finding is in keeping with the important functional role of the centrally localized mature macrophages during erythropoiesis. A relevant pretransplant reduction of the red cell lineage and an early to advanced reticulin fibrosis were correlated with a low hemoglobin level (anemia) and splenomegaly and furthermore associated with a significant delay to reach transfusion independence. This result was supported by corresponding findings in biopsy specimens performed shortly after day 30 following BMT (standard interval for assessment of engraftment). Samples revealed an enhancement of fiber density and a conspicuous decrease in the amount of erythropoiesis in the small fraction of patients who did not conform with the usually accepted criteria for successful hematopoietic reconstitution. Considering the compartment of histiocytic reticular cells the recurrence of Pseudo-Gaucher cells (PCGs) in the engrafted donor marrow was remarkable and most prominently expressed in the first two months following BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in the sequel of myelo-ablative therapy (scavenger macrophages). According to planimetric measurements in the postgraft bone marrow the atypical dwarf-like CD61+-megakaryocytes characteristic for CML disappeared. On the other hand, normalization of megakaryocyte size and nuclear lobulation were absent in sequential examination of the few patients developing a leukemic relapse. In a number of patients with manifest myelofibrosis at onset, an initial regression after BMT was followed by an insidiously occurring retrieval which was concentrated on the areas of reconstituting hematopoiesis. Similar to its relevant pretransplant association the postgraft reappearance of myelofibrosis was significantly correlated with the quantity of CD61+-megakaryocytes. Altogether a number of histological features in the pre-and postgraft bone marrow exhibited significant correlations with each other and thus indicated functional relationships. Moreover, quantity of erythropoiesis and amount of reticulin fibers (myelofibrosis) exerted a significant impact on engraftment status.
 ...
PMID:Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients. 1119 98

An immunohistochemical and morphometric study was performed on 363 trephine biopsies of the bone marrow derived from 127 patients with chronic myeloid leukemia at standardized end points before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate features of CD61+ megakaryopoiesis related to successful engraftment. Further, we tried to elucidate possible associations of this lineage, including precursor cells, with the platelet count and reticulin fibrosis during the pretransplant and, specifically, post-transplant periods. A significant correlation was recognizable between the quantity of CD61+ megakaryocytes and the platelet values before BMT and also after completed hematopoietic recovery. In the very early post-transplant period, which is associated with severe thrombocytopenia, patchy regeneration of disarranged hematopoiesis occurred, including dysplastic megakaryocytes. According to planimetric measurements after BMT, the atypical micromegakaryocytes characteristic for chronic myeloid leukemia disappeared, and the engrafted donor bone marrow revealed a prevalence of normal-size cells of this lineage. On the other hand, normalization of megakaryocyte size was absent in sequential examinations of the few patients with a leukemic relapse who had a predominance of atypical dwarf forms comparable with chronic myeloid leukemia. Before BMT occurred, reticulin fiber density was significantly correlated with the number of CD61+ megakaryocytes and its precursor cell population. In 34 patients with myelofibrosis that occurred after myelo-ablative therapy and BMT, an initial regression was followed by an insidious recurrence of fibers concentrated in the areas of regenerating hematopoiesis. This postgraft reappearance of reticulin fibrosis was significantly associated with the quantity of megakaryocytes. Regarding engraftment parameters, pretransplant presence of (reticulin) myelofibrosis exerted a distinctive impact because of a delayed hematopoietic reconstitution according to standard clinical criteria. In line with this finding, slowed engraftment was also significantly related with higher pretransplant megakaryocyte and platelet counts.
 ...
PMID:Megakaryopoiesis and myelofibrosis in chronic myeloid leukemia after allogeneic bone marrow transplantation: an immunohistochemical study of 127 patients. 1123 4

The myeloproliferative disorders (MPDs) are a group of pre-leukaemic disorders characterized by proliferation of one or more lineages of the myelo-erythroid series. Unlike the Philadelphia chromosome in chronic myeloid leukaemia, there is no pathognomonic chromosomal abnormality associated with the MPDs. Chromosomal abnormalities are seen in 30-40% of patients with polycythaemia vera (PV) and idiopathic myelofibrosis (IMF) and seem to indicate a poor prognosis. On the other hand, chromosomal abnormalities are rare in essential thrombocythaemia. Consistent acquired changes seen at diagnosis include deletion of the long arm of chromosome 20, del(13q), trisomy 8 and 9 and duplication of parts of 1q. Furthermore del(20q), trisomy 8 and dupl(lq) all arise in multipotent progenitor cells. Molecular mapping of 20q deletions and, to some extent, 13q deletions has identified a number of candidate target genes, although no mutations have yet been found. Finally, translocations associated with the rare 8p11 myeloproliferative syndrome and other atypical myeloproliferative disorders have permitted the identification of a number of novel fusion proteins involving fibroblast growth factor receptor-1.
 ...
PMID:Myeloproliferative disorders. 1164 Aug 68

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.
 ...
PMID:Mixed chimerism of bone marrow vessels (endothelial cells, myofibroblasts) following allogeneic transplantation for chronic myelogenous leukemia. 1268 52

The expression of 82 cell surface molecules was analysed on pathological cells from 52 patients with acute lymphoblastic leukemia (T and B), acute myeloid leukemia (FAB: M0, M1, M2, M3, M4, M5), chronic myeloid leukemia, chronic myelo-monocytic leukemia) and non Hodgkin's lymphoma (T and B types). We have selected patients with a high leukocyte count and percentage of blasts. Staining for membrane molecules was done by the immunofluorescence method and evaluated by flow cytometry. The findings indicate that expression of membrane molecules on pathological cells is quantitatively and qualitatively different in individual cases. The leukemia/lymphoma cells in their crude from represent the main phenotypes of normal haematopoietic cells, which reveal the great diversity of immunophenotypes within the main functional characterization of blood malignancies. The immunophenotype heterogeneity of leukemic cells has proved to be much greater than the match with existing classification criteria, this fact could raise the necessity for further functional evaluation and specification of immunophenotyping of the leukemia/lymphoma cells. The concept of explanation of pathogenesis and pathophysiology of different types of leukemia/lymphoma cells on the basis that they are derived from normal haematopoiesis must be accepted, because the number of membrane markers and their functional properties are correspondingly convincing.
 ...
PMID:The interaction and functional properties of leukocyte molecules of human leukemia/lymphoma cells. 1457 28

The WT1 gene is considered to be highly expressed in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia and is thought to play a key role in maintaining the viability of leukemia cells. However, little is known about the WT1 gene expression levels in pediatric patients with juvenile myelo-monocytic leukemia (JMML) and myelodysplastic syndromes (MDS). We studied WT1 expression in diagnostic bone marrow (BM) and peripheral blood (PB) samples of 90 patients with JMML, low grade MDS, advanced MDS and myelodysplasia-related AML in BM (n = 20) and PB (n = 18) samples of normal healthy volunteer donors.
 ...
PMID:WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelo-monocytic leukemia? 1518 34

We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984-1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia.
 ...
PMID:Hematological malignancies in the island of Sardinia, 1974-1993: age and sex distributions and temporal changes in incidence. 1599 Dec 20


<< Previous 1 2 3 4 5 Next >>