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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of serum from patients with chronic myeloid leukemia (CML) in both chronic phase and blastic transformation, to agar cultures of normal human marrow cells stimulated the growth of persisting colonies (day 35) containing either eosinophils or mast cells. Chronic phase serum stimulated an 800% increase in the total number of these colonies of which only 16% were mast cells. Serial studies using serum from 2 patients demonstrated that the proportion of mast cells increased during the progression to blastic transformation. The emergence of a greater proportion of persisting mast cell colonies and a decrease in absolute number of eosinophil colonies in agar cultures of normal marrow cells containing serum from patients with CML coincides with the emergence of blastic transformation and suggests that a significant change occurs in the absolute and relative concentration of hemopoietic growth factors in these patients.
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PMID:Persisting colonies in agar cultures containing serum from patients with CML in blastic transformation. 347 81

Cord plasma contains colony-stimulating activity (CSA) which stimulates the in vitro clonal growth of neutrophils, eosinophils, macrophages, erythrocytes, and persisting mast cells in semisolid cultures. Analysis of day 35 colonies in agar cultures was found to be a suitable means of demonstrating this activity and discriminating between it and granulocyte-macrophage colony-stimulating factor (GM-CSF). Serum (10%) from patients with acute and chronic myeloid leukemia (AML and CML) was added to normal human bone marrow cultures to search for similar activity in these patient's serum. Although the number of colonies on day 12 (predominantly neutrophils and macrophages) was not significantly different from the number of colonies in cultures containing normal serum, the number of colonies increased 500% in cultures containing CML serum on day 35. Serum from patients with AML during regeneration also stimulated an increased number of colonies on day 35. Although both eosinophil and mast cell colonies were still present on day 35, only mast cell colonies persisted for 150 days. On day 35, cultures containing 10% CML serum contained predominantly eosinophil colonies (84%), whereas cultures containing AML serum contained predominantly mast cell colonies (76%). Although serum contains various CSFs, the specific factor which stimulates persisting mast cell colonies may be the human equivalent of murine persisting (P) cell-stimulating factor (Multi-CSF).
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PMID:Stimulation of persisting colonies in agar cultures by sera from patients with CML and AML. 348 60

The authors report a patient with Ph1-positive chronic granulocytic leukemia (CGL) who developed "blast crisis" after six years of chronic phase. The presence of mast cell precursors and basophil blasts was demonstrated by ultrastructural morphology and cytochemistry. Membrane phenotype studies with monoclonal antibodies helped in the further characterization of these cells. The possible implication of these findings in the origin of mast cells and the relationship of these cells with basophils are discussed.
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PMID:Blast crisis of chronic granulocytic leukemia with mast cell and basophilic precursors. 385 96

The neoplastic proliferation of tissue mast cells constitutes a group of rare diseases that have localized and systemic variants. The cytologic (n = 7) and histologic (n = 38) findings in bone marrow from a total of 45 patients with systemic mastocytosis were evaluated. Three distinct histologic patterns of marrow involvement were distinguished. In 21 cases a patchy or focal infiltration pattern was encountered. Mast cell aggregates were located predominantly in peritrabecular and perivascular areas. The adjacent trabeculae were thickened. A dense network of reticulin fibers and foci of lymphocytes accompanied the mast cell infiltrates. Increased numbers of eosinophils frequently demarcated the mast cell infiltrates from the surrounding tissue. In the noninfiltrated marrow areas hematopoiesis and the distribution of fat cells appeared to be normal. This histologic pattern, designated type 1, was observed exclusively in patients showing primary involvement of the skin, indistinguishable from urticaria pigmentosa. In 14 additional cases peritrabecular and perivascular sheets of mast cells, with concomitant fibrosis and osteosclerosis, were also present. Unlike the findings in type 1, however, the noninfiltrated marrow areas showed marked reductions in fat cell content and markedly increased granulocytopoiesis or increased numbers of blast cells (infiltration pattern type 2). On the basis of the hematologic and clinical findings, chronic myeloid leukemia was diagnosed in six of these cases, myelomonocytic leukemia in three cases, and acute myeloid leukemia in two cases. The bone marrow of three patients was diffusely infiltrated by atypical mast cells, leading to marked hypoplasia of fat cells and blood cell precursors. These histologic features were identified as infiltration pattern type 3. The diagnosis of mast cell leukemia was confirmed in all three cases by the presence of numerous mast cells in the blood. The prognosis for patients with the type 1 marrow infiltration pattern and primary skin involvement was favorable (actuarial survival rate five years after diagnosis, 0.75). This variant was called benign systemic mastocytosis. Primary skin involvement did not occur in the patients with type 2 or 3 infiltration patterns. The prognosis for these patients was poor (actuarial survival five years after diagnosis, 0.17 for type 2 and 0.00 for type 3). These two forms were accordingly designated malignant systemic mastocytosis.
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PMID:Bone marrow findings in systemic mastocytosis. 386 Apr 69

The demonstration and frequency of mixed granulated, hybrid leukocytes in chronic myeloid leukemia are reported. The cells exhibit basophilic granules, and, in addition, variable quantities of eosinophilic and/or azurophilic (chloroesterase-positive) granules. The existence of further subtypes of granules in these cells, such as neutrophilic or tissue mast cell granules, cannot be excluded thus far. All cases under investigation showed such cells, though in varying frequency. Quality and quantities of the granule population in these cells differed considerably. This is interpreted as an expression of tumor cell heterogeneity, which represents a general criterion of malignant neoplasias. The cells under discussion may be termed hybrid or chimeric, since they are characterized by the co-expression in the same cells of markers (granules) normally subject to lineage specificity. Therefore, the cells represent the phenomenon of "lineage infidelity". Thus far, "lineage infidelity" has been found only with blast cell leukemias, but applies also to chronic myeloid leukemias, as our results show. The occurrence of "lineage infidelity" in segmented end stage cells expresses grave irreversible genetic disturbances of the differentiation program in the progenitors of the hybrid leukocytes.
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PMID:[Recognition and significance of hybrid granulocytes in chronic myeloid leukemia]. 386 44

Systemic mast cells disease (SMCD) is an uncommon disorder that constitutes approximately 10% of all mastocytoses. Diagnosis requires a substantial degree of clinical suspicion, which may not be present if characteristic skin lesions of urticaria pigmentosa are not observed. Lack of well-defined histopathologic features for the disease have delayed or prevented the diagnosis of SMCD. An initial diagnosis of "myeloproliferative disorder," chronic granulocytic leukemia, or myelofibrosis is frequently made. Study of the clinical and pathologic features of 26 cases of SMCD indicated that affected patients are generally middle aged and may have had urticaria pigmentosa for many years. Gastrointestinal symptoms are common, and splenomegaly and hepatomegaly along with radiographic evidence of generalized bone disease are usually noted. Hematologic factors are highly variable. Characteristic histopathologic features of SMCD are described for bone marrow, lymph nodes, liver, and spleen. The authors consider tissue fixation and staining methods to help identify mast cell lesions.
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PMID:Systemic mast cell disease: a clinical and hematopathologic study of 26 cases. 617 98

Ultrastructural and ultracytochemical studies were performed on blood and bone marrow specimens from 18 patients with Philadelphia chromosome-positive blastic leukemia; 7 patients were in blast transformation following a typical history of chronic myelogenous leukemia and 11 patients presented with "acute leukemia." The patients were divided into 2 morphologic groups on the basis of light microscopic and cytochemical observations. In group I, which consisted of 11 patients, the proliferating cells were "lymphoid" in appearance and demonstrated many cytochemical, biochemical, and immunologic features similar to those of the lymphoblasts of non-T, non-B acute lymphoblastic leukemia. In group II, which consisted of 7 patients, the proliferating cells were myeloid in appearance. On the basis of ultrastructural observations, the 11 group I patients were divided into 2 subgroups, A and B. Subgroup IA, consisting of 5 patients, was characterized by blasts that demonstrated no differentiating features. In subgroup IB, consisting of 6 patients, 20-30% of the leukemic cells contained inclusions that resembled leukemic mast cell or basophil granules. The leukemic cells in the 7 group II patients manifested myeloid characteristics by light microscopy and prominent basophil and mast cell granulopoiesis by electron microscopy. Abnormalities of other myeloid cell lines were also observed in both the lymphoid and myeloid groups of patients.
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PMID:Ultrastructural features of basophil and mast cell granulopoiesis in blastic phase Philadelphia chromosome-positive leukemia. 693 33

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.
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PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

Constitutive activation of the Abelson (Abl) protein tyrosine kinase (PTK) is a causative event in chronic myeloid leukemia, where intense chemotherapy currently fails to eradicate the leukemic clone. Using a mouse mast cell line (IC.DP), we previously showed that v-Abl PTK induced resistance to the anti-cancer drugs melphalan and hydroxyurea by the suppression of apoptosis. Here, using this cell line, we demonstrate by alkaline elution that v-Abl PTK did not affect the levels of DNA damage induced by either drug. This confirms that v-Abl PTK acts downstream of the drug-target interaction to prevent the coupling of drug-induced damage to the apoptotic pathway. Although Abl PTK- and interleukin-3 (IL-3)-stimulated signaling events share common signaling pathways, a similar level of drug resistance was not provided by IL-3, implying that Abl PTK does not merely mimic an IL-3 survival signaling pathway. Previously we demonstrated translocation of protein kinase C-beta II stimulated by activation of Abl PTK. Drug sensitivity was restored in cells with active v-Abl PTK by simultaneous addition of calphostin C, an inhibitor of protein kinase C, suggesting a role for protein kinase C in the suppression of drug-induced apoptosis by v-Abl PTK. One novel strategy for the treatment of chronic myeloid leukemia could therefore include the use of a downstream modifier of the Abl PTK-mediated survival signaling pathway to render leukemic cells more sensitive to a second drug, such as a cytotoxic agent.
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PMID:Characterization of drug resistance mediated via the suppression of apoptosis by Abelson protein tyrosine kinase. 765 67

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favourable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The larynx in lymphoproliferative and myeloproliferative diseases. Part II: Laryngeal autopsy findings and discussion]. 792 29


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