Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD44 cell surface proteoglycan participates in a variety of functions including lymphohematopoiesis, lymphocyte homing and tumor metastasis. In addition to the standard form (CD44st), a large family of variant isoforms (CD44v) is generated by alternative splicing of a single gene. Certain CD44v (v5 and V6) are upregulated in the course of neoplastic progression and reflect the metastatic potential of tumor cells. CD44 v6 is expressed in high-grade non-Hodgkin's lymphoma cells and is released in the serum, thus providing a soluble marker that reflects tumor burden, disease progression and treatment response. Here we show that serum CD44st is elevated in approximately half of B-CLL patients. In contrast, CD44v5 and v6 are detected at normal levels in the large majority of the cases. CD44st serum levels correlate significantly with the number of circulating leukemic B cells and with the levels of another soluble B-CLL marker, beta2-microglobulin. Immunoprecipitation analyses of B-CLL sera allow detection of several high molecular weight bands and of a 78 kDa band that represents a soluble form of CD44st and is 4 kDa lower than a similar band (82 kDa) detected in B-CLL cell lysates. Elevated serum CD44st associates with a number of unfavorable prognostic factors such as high peripheral blood lymphocytosis, splenomegaly, advanced disease stage and therapy requirement. A follow-up study indicates that serum levels of CD44st are related to disease status, thus reinforcing our veiw that this molecule may represent a reliable tumor marker in B-CLL.
Leukemia 1997 Jan
PMID:Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia. 900 29

In 1992, after a history of more than two decades a subgroup within the diffuse low-grade B cell lymphomas designated centrocytic lymphoma, lymphocytic lymphoma of intermediate differentiation or mantle zone lymphoma gained general acceptance, now referred to as mantle cell lymphoma. Similarities between these entities were emphasized by identification of rearrangement and overexpression of CCND1 (bcl1/PRAD1) gene in the majority of cases. Unlike in all other non-Hodgkin's lymphomas sex distribution demonstrates a striking preponderance of males over females with a ratio of 3:1. Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients. In generalized disease, clinical course is characterized by continuous progression with a median survival probability of 3-4 years within most series. Overall response rates of 56-88% with complete remissions in the range of 9-58% are attainable but relapse occurs predominantly within 20 months. At present there is no evidence that any conventional regimen is curative. Prospective multicenter studies are mandatory to overcome this therapeutic dilemma. Patients suitable for some form of maintenance or consolidation therapy should initially be treated intensively by anthracycline-containing regimens. Whether maintenance with interferon or intermittent chemotherapy including new agents, like purine analogues or (un)conjugated monoclonal antibodies are able to influence overall survival is a matter of (ongoing) investigations. Further experimental approaches arise from antisense oligonucleotides or ribozymes blocking the overexpression of bcl-1 especially in this lymphoma entity. At present high-dose myeloablative consolidation radiochemotherapy followed by stem cell rescue in first remission seems to be the most attractive option in younger patients.
Leukemia 1997 Apr
PMID:Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems. 917 43

We report the clinical, ultrastructural, immunophenotypic and virological features of nine cases of a rare type of mature T cell disorder formerly designated Sezary cell leukaemia. All patients presented with lymphocytosis ranging from 12.7 to 133 x 10(9)/l, bone marrow infiltration, splenomegaly and lymphadenopathy. Skin involvement was absent at presentation but developed as a terminal event in two patients, one of whom showed a pattern of dermal infiltration different from that characteristic of Sezary syndrome. Cells from eight cases bore a mature T cell phenotype and electronmicroscopy revealed lymphocytes with cerebriform nuclei resembling Sezary cells. All cases except one were HTLV-I negative. Patients were treated with various chemotherapy regimens but with poor outcome, the median survival being 13 months. Laboratory and clinical data suggest great similarity between Sezary cell leukaemia and T prolymphocytic leukaemia (T-PLL), namely coexpression of CD4 and CD8 (3/9 cases), identical chromosomal abnormalities in the three cases studied (isochromosome 8q plus inversion 14 or t(X;14)(q28;q11)) and a remarkable sensitivity to CAMPATH-1H (complete remission of 21 months' duration in one patient), suggesting that this entity could be considered a variant form of T-PLL. The alternative diagnosis of adult T cell leukaemia/lymphoma could not be excluded in one patient in whom positive HTLV-I serology was documented.
Leukemia 1997 Jul
PMID:Sezary cell leukaemia: a distinct T cell disorder or a variant form of T prolymphocytic leukaemia? 920 83

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the HTLV-I pX gene under control of the mouse H-2Kd promoter, mammary carcinomas developed predominantly in females starting at about 5 months of age. The incidence of the tumor reached about 40% when the rats were 12 months old. Histology of the tumor was undifferentiated carcinoma with massive infiltration of granulocytes into the tumor tissue. Systemic granulocytosis and hepato-splenomegaly due to extramedullary granulocytopoiesis were seen in pX rats and nude mice bearing pX mammary tumor. mRNAs of both pX and host genes, Gro and MIP-2, which are granulocyte chemoattractants of the IL-8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and anti-oncogene, related with mammary carcinomas, were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats. pX mammary carcinoma cell lines, which have similar characteristics to the primary tumor, were established and the cells underwent apoptosis under the serum deprived conditions. The pX rats and the pX mammary carcinomas appear to be suitable models for analyses of HTLV-I pX oncogenesis and immune pathogenesis in vivo and in vitro.
Leukemia 1997 Apr
PMID:HTLV-I pX transgenic rats: development of cytokine-producing mammary carcinomas and establishment of the pX mammary carcinoma cell lines. 920 2

We describe the clinical and laboratory features of an unusual case with Sezary cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly. There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine showed diffuse infiltration by atypical lymphoid cells. By ultrastructural analysis the cells were small to medium-size lymphocytes with nuclear features identical to Sezary cells. Immunophenotyping showed that most peripheral blood mononuclear cells were negative with B lymphoid, myeloid, and stem cell-associated markers and were also negative with most T lymphoid markers (CD2, CD4, membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38 (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal rearrangement of the TCR beta and gamma chain genes. The patient was initially treated with vincristine, doxorubicin and asparaginase and then with six cycles of CHOP, achieving a complete remission and remaining free of disease 22 months from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell-like leukemia, in which cells lacked most of the T cell-associated antigens.
Leukemia 1997 Aug
PMID:Sezary cell-like leukemia with atypical immunophenotype. 926 98

Agnogenic myeloid metaplasia (AMM) is a disease characterized by bone marrow megakaryocyte hyperplasia and clusters of megakaryocytes, in which many of the megakaryocytes are atypical. In order to elucidate the mechanisms of megakaryocytosis, ELISA assays of blood levels of thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11) were done in 45 patients with AMM and compared with normal volunteer controls. Higher blood TPO levels were found in AMM than in controls (P < 0.0001), and blood TPO levels were correlated with the degree of marrow fibrosis (P = 0.0078). Blood levels of IL-6 were also significantly higher in AMM, when compared with controls (P < 0.0001). However, no correlation was found between blood IL-6 levels and degree of marrow fibrosis. No correlation was found between either TPO or IL-6 and the number of blood platelet counts, the number of marrow megakaryocytes, WBC counts, or the degree of splenomegaly. Blood IL-11 levels were undetectable in most patients and no significant difference was found in AMM as compared to controls. The present study demonstrated that, while in idiopathic thrombocytopenic purpura (ITP) or aplastic anemia, blood TPO levels are relatively correlated with the numbers of platelet and/or megakaryocyte mass, blood TPO levels do not correlate with blood platelet counts, or marrow megakaryocyte mass in AMM. Therefore, in AMM, other mechanisms such as the number of TPO receptors on platelets or megakaryocytes, c-MPL receptor abnormalities, abnormal production of TPO mRNA and so on, will have to be studied. Furthermore, TPO may play a significant role in the pathogenesis of marrow fibrosis; IL-6 may be a factor in the development of marrow megakaryocytosis but its elevated blood levels may represent a secondary immune phenomenon; and IL-11 probably does not play a significant role in causing marrow megakaryocytosis in this disease.
Leukemia 1997 Nov
PMID:Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia. 936 14

Although the presence of a chromosome 11q23 breakpoint is of recognized poor prognosis in acute lymphoblastic leukemia, its prognostic significance in acute myeloid leukemia (AML) has been the object of conflicting reports, perhaps reflecting the possibility of different entities. It has been found that only typical and generally balanced 11q23 chromosomal anomalies involve the MLL gene while atypical and generally unbalanced do not. To determine whether these two categories of AML patients had different initial characteristics and evolution, supporting different pathogenetic mechanisms, we analyzed clinical and biologic characteristics of newly diagnosed AML patients with balanced 11q23 breakpoint and/or MLL rearrangement seen over a 10-year period in our institution and compared them to cases with unbalanced 11q23 anomaly seen over the same period. These two categories of patients were compared with newly diagnosed patients with normal karyotype and no MLL rearrangement when tested, seen over the same period of time and treated similarly. Over this period, 442 newly diagnosed adult (> 15 years) AML seen in our institution had a successful karyotype performed before any therapy. Thirty-six cases (8%) had a chromosome 11q23 breakpoint including 19 cases with a balanced translocation or inversion and 17 cases with an unbalanced anomaly. Eighty-seven recently diagnosed cases of AML, for whom frozen cellular material was available, were analyzed by Southern blot for the presence of MLL gene rearrangement. Fourteen cases (16% of the tested cases) had a rearrangement of the MLL gene, including seven cases with an apparently successful karyotype not showing any 11q23 breakpoint and two cases with no available karyotype. The only case with unbalanced 11q23 chromosomal anomaly which was tested had no MLL rearrangement. There was a clear-cut clinical difference between the 28 patients having a balanced 11q23 anomaly/MLL rearrangement and the 17 patients having an unbalanced chromosomal anomaly: AML with unbalanced 11q23 anomalies occurred in older patients (P = 0.07) tended to be less frequently associated with previous exposure to topoisomerase II-active drugs and with M4/M5 FAB cytological subtypes, were always associated with other chromosomal anomalies (P < 0.0001), expressed more frequently the CD34 antigen (P = 0.05) and were of considerably poorer prognosis for achievement of CR (P = 0.005) and survival (P = 0.0005). When compared to the control population, patients with balanced anomalies had more frequent history of toxic exposure (P = 0.0003) particularly to topoisomerase II-active drugs, tended to be more frequently of M4/M5 FAB subtypes (P = 0.07), expressed more frequently HLA-DR antigen (P = 0.02) and had shorter DFS (P = 0.02). Patients with unbalanced anomalies had more frequent splenomegaly (P = 0.009), lower WBC count (P = 0.04), and much poorer prognosis for CR achievement (P = 0.0001), survival (P < 0.0001) and DFS (P = 0.01). This study confirms the high frequency of 11q23 chromosomal breakpoint/MLL rearrangement in adult AML and the probable existence of two different entities with different clinical features according to the presence of a balanced or unbalanced cytogenetic abnormality, the latter being not associated with MLL rearrangement.
Leukemia 1998 Jan
PMID:Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint. 943 17

In west Africa, splenic lymphoma with villous lymphocytes and hyper-reactive malarial splenomegaly have many clinical and immunological features in common suggesting an aetiopathological link. We hypothesize that in hyper-reactive malarial splenomegaly the dysregulated immune response to repeated malaria infections results in a stimulated, proliferating pool of B cells in which perturbation of cell growth and apoptosis by environmental and other factors promotes the development of SLVL. In Africa these factors are likely to include infectious agents several of which have already been associated with B-cell non-Hodgkin's lymphomas.
Leukemia 1997 Dec
PMID:Chronic malaria and splenic lymphoma: clues to understanding lymphoma evolution. 944 36

A 54-year-old woman presented with a severe autoimmune anemia, thrombocytopenia, neutropenia (Evans' syndrome), and CD8+ lymphocytosis, without signs of lymphadenopathy or splenomegaly. A diagnosis of T cell large granular lymphocyte (T-LGL) leukemia was made, based on cytomorphology, the typical CD3+/CD4-/CD8+/CD16+/CD56-/CD57-/HLA-DR(+/-) immunophenotype of the lymphocytosis (9 x 10(9)/l), and biallelic clonally rearranged T cell receptor beta (TCR beta) genes. Clonality of the TCR alphabeta+ T-LGL was also demonstrated with a panel of antibodies against variable domains of TCR beta chains, which showed single Vbeta7.1 expression on the CD3+ T-lymphocytes. After treatment failure with corticosteroids, splenectomy, and cyclophosphamide, respectively, a complete clinical remission was induced and sustained with cyclosporin A. Vbeta7.1/CD8/CD3 triple immunofluorescence stainings appeared to be valuable for titrating the cyclosporin A dosage by monitoring the T-LGL cells during treatment.
Leukemia 1998 Feb
PMID:Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vbeta antibodies. 951 76

To date, neither the clinical significance of isolated trisomy 8, the most frequent trisomy in acute myeloid leukemia (AML), nor the effect of age within a single cytogenetic group has been examined. We report a large cohort of adult trisomy 8 patients and examine whether increasing age within a homogeneous cytogenetic group alters clinical outcome. Characteristics and outcome of patients with isolated trisomy 8 enrolled in the prospective Cancer and Leukemia Group B (CALGB) cytogenetic study CALGB 8461 are described. Isolated trisomy 8 was identified in 42 (3.03%) of 1387 patients enrolled in five CALGB treatment protocols. These patients had a median age of 64 (range, 16-79) years, 50% female proportion, and a low frequency of hepatomegaly (10%) or splenomegaly (10%). Laboratory features included a median white blood count of 7.3 x 10(9)/L, nonspecific French-American-British distribution, with 36% of patients having Auer rods. Treatment outcome was unsatisfactory with a complete remission (CR) rate of 59%, median CR duration of 13.6 months, and median survival of 13.1 months. Older age adversely affected outcome; trisomy 8 patients > or =60 years had both an inferior CR rate (40% versus 88%; P = 0.004) and overall survival (median, 4.8 versus 17.5 months; P = 0.01), as compared with those <60 years of age. Of the patients <60 years of age, only four remain alive, and all received noncytarabine-based intensive chemotherapy, followed in three cases by autologous (n = 2) or allogeneic (n = 1) stem cell transplant in CR1. Adults with AML and isolated trisomy 8 have a poor outcome that is accentuated by increasing age and is rarely cured with cytarabine-based therapy. Alternative investigational treatments should be considered for individuals with this AML subset.
 ...
PMID:Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461. 960 82


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