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

A case of a 37-year-old woman presenting with acute agnogenic myeloid metaplasia (AAMM) is described. The disease had a stormy course and was characterized by moderate splenomegaly, persistently depressed WBC counts, extramedullary hemopoiesis and presence of a high percentage of atypical myeloblasts in the peripheral smear. Platelets were persistently low, reticulocytes significantly below normal, notwithstanding anemia. Hot tended to fall progressively to intolerably low values in the absence of transfusion. The chromosomal mapping of peripheral blood revealed the presence of a trisomy of chromosome No. 8. This abnormality already demonstrated in two previous cases of acute myelofibrosis and the clinical course of the disease suggest that acute myelofibrosis and AAMM could be the same disease while chronic myelofibrosis should be considered a separate entity. Also, it is possible that AAMM with trisomy of chromosome No. 8 and stormy clinical course may be a different entity from the acute myeloproliferative disorders associated with other chromosomal abnormalities.
 ...
PMID:Acute agnogenic myeloid metaplasia with chromosomal abnormalities. 11 13

We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55-year-old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50--95% myeloblast cells and 95--100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,-6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated 90% of metaphases by autoradiography. The second patient, a 49-year-old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,-13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.
 ...
PMID:Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera. 60 27

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.
 ...
PMID:[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML]. 163 23

Subcutaneous inoculation of Epstein-Barr virus (EBV) transformed peripheral blood B-lymphocytes (PBL) from an untreated chronic lymphocytic leukemia (CLL) patient produced progressively growing lethal tumors in 4 of 11 whole body irradiated (440 rads) nude mice. In one tumor bearing mouse there was splenomegaly and generalized enlargement of lymph nodes. Chromosomal analysis and membrane immunofluorescence revealed that cells in all the 4 s.c. tumors and a proportion of cells in the enlarged spleen and lymph nodes had human chromosomes and contained human kappa or lambda chains demonstrating that these were polyclonal human B-cells. Epstein-Barr virus associated nuclear antigen could be detected in 100% of cells in all the 4 EBV transformed B-cell lines in vitro and aliquots of cells from several s.c. tumors and metastatic lesions examined. Successful serial transplantation into irradiated nude mice was possible for at least 3 generations with one of the 4 s.c. tumors. During serial transplantation, spread of tumor cells to the spleen and lymph nodes could be detected in all the 3 passage mice investigated; however, there was no evidence in any mouse of dissemination of tumor cells into the bloodstream or into any organ other than lymph nodes and spleen. s.c. tumors also developed in a proportion of irradiated nude mice after inoculation of cells from two other s.c. tumors and the metastatic spleen and lymph nodes, but all these tumors regressed during the first or second transplant passage. Two % of PBL from the untreated patient and 4% of EBV transformed PBL maintained in vitro were found to have trisomy of chromosome 12 which is the most frequently reported anomaly associated with human CLL B-cells. It is highly probable that the cells with trisomy were derived from the leukemic clone of this patient. Cells with this trisomy predominated in most metastatic sites compared to the parent s.c. tumors. Inoculation of irradiated nude mice with EBV transformed PBL from this patient after chlorambucil therapy (100% metaphase plates with 46,XY,11q+ karyotype) or with EBV transformed PBL from 2 normal adults failed to produce any progressively growing tumor in a total of 12 irradiated animals observed greater than 300 days. Although there are several reports of EBV induced immortalization of CLL B-cells in vitro, we have not seen any previous report on the successful serial transplantation and dissemination of EBV transformed CLL B-cells in nude mice.
 ...
PMID:Growth and spread in nude mice of Epstein-Barr virus transformed B-cells from a chronic lymphocytic leukemia patient. 300 90

There have been many reports of cases in which chronic increases in the numbers of natural killer (NK) cells have been reported. Whether this is reactive or neoplastic in nature has been debated. We report the first case of an aggressive NK cell leukemia in an adult with establishment of an NK cell line. A 70-year-old man had two spontaneous episodes of jejunal perforation and one month later developed a severe febrile illness with moderate splenomegaly. Hemoglobin was 13.1 g/L, and WBC count was 1.8 X 10(9)/L with 2% large granular lymphocytes (LGLs). Platelet count was 143 X 10(9)/L; prothrombin time (PT) and partial thromboplastin time (PTT) were normal. Bone marrow was infiltrated with 25% to 30% LGLs; serum lysozyme was normal. Serum LDH was initially 1,191 U/L and rose to 6,408 (normal 240 to 525 U/L). Ten days later, the WBC count increased to 99.9 X 10(9)/L with 70% LGL cells; the PT and PTT increased, and the platelet count dropped. No bacterial or viral cause of fever was identified. The cells from peripheral blood were LGLs that stained positively for acid phosphatase. All of the LGLs reacted with a monoclonal antibody reactive with NK cells (LEU-11b). Functionally, the patient's peripheral blood mononuclear cells (PBMs) demonstrated 100 times more lytic activity against K562 tumor cell lines than did normal PBMs. The patient's PBMs were propagated in vitro. The cultured cells showed the morphological, cytochemical, immunological, and functional characteristics of NK cells. In addition, partial trisomy involving chromosome 1 q with duplication in regions of q21 through q31 was observed in all metaphases analyzed. The extra chromosome 1q with duplication in regions q21 through q31 was translocated to the p-terminal of chromosome 5. One percent to 5% of normal PBMs comprise NK cells; in most cases, leukemias arise from normal phenotypic counterparts. This case demonstrated that aggressive NK cell leukemia may occur in adults. In addition, the chromosomal abnormalities suggest that this is not a reactive process but a malignancy.
 ...
PMID:Aggressive natural killer cell leukemia in an adult with establishment of an NK cell line. 395 37

Cytogenetic studies (CG) of 475 chronic lymphocytic leukemia (CLL) cases showed trisomy 12 in 6.1% or 26% of patients with abnormal karyotypes. Fluorescence in situ hybridization (FISH) detected trisomy 12 in 35% of 117 CLL patients. Only 34.6% of cases detected by FISH were detected by CG. Twelve patients had low levels of trisomic cells (4% to 11%) relative to clonal B cells (47.5% to 86%), suggestive of clonal evolution. Untreated patients with trisomy 12 were predominantly male (P < .05) and had an increased incidence of splenomegaly (P < .03). Patients with trisomy 12 were more likely to be previously treated and had advanced Binet stage compared with those without trisomy 12. The median survival was shorter in patients with trisomy 12 (7.8 years) and patients with other chromosomal abnormalities without trisomy 12 by FISH (5.5 years) than in patients with diploid karyotypes (14.4 years). The response to fludarabine was similar to that of patients with diploid karyotypes, but there was a trend for earlier disease progression. FISH detected residual disease in all patients with trisomy 12 in complete (n = 6) or partial remission (n = 4). As few as 1 trisomic cell in 5,000 was detected by performing FISH on fluorescence-activated cell sorter-sorted cells. Trisomy 12 was absent in T cells in patients with trisomy 12. We conclude that FISH identifies trisomy 12 approximately 2.6 times more often than CG, readily identifies minimal residual disease, and predicts for a shorter median survival.
 ...
PMID:Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia. 768 27

Fluorescence in situ hybridization (FISH) with a chromosome 12 specific alpha-centromeric probe was performed on interphase cells from 183 patients with B-cell chronic lymphocytic leukemia (CLL). Twenty one cases with trisomy 12 (11.5%) were detected. The number of trisomic cells ranged from 5.5% to 76% (mean 38.5%). No correlation was found between the presence of trisomy 12 and white blood cell count, hemoglobin level, platelet count, a specific immunophenotype, clinical stage, sex, splenomegaly, or lymphadenopathy. Morphologic review of all cases with trisomy 12 showed seven (33%) with more than 10% prolymphocytes and three (14%) with CLL of mixed cell type. While trisomy 12 is the most common chromosomal abnormality in CLL, it is more frequent in morphologically atypical cases, some of which may be undergoing transformation. There was a statistically significant difference in the incidence of atypical cases between those with (47%) and without (7.6%) trisomy 12 (P < .001). It remains to be determined whether this abnormality is associated with a worse prognosis; this is currently being investigated in the context of a national therapeutic trial. The technique used is more sensitive than conventional cytogenetic analysis, which in this series failed to detect trisomy 12 in six cases. FISH allows the systematic study on a large number of patients without the need of metaphase preparations.
 ...
PMID:Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: analysis by stage, immunophenotype, and morphology. 768 64

A series of 20 patients with granular lymphocyte proliferative disorders (GLPD) is reported. The criterion of inclusion was presence of persistent (> or = 6 months) granular lymphocytosis in the absence of any causative illness. Diagnoses made upon analytical control in half the patients of splenomegaly (25%) and hepatomegaly (25%) were infrequent. Clinical course was nonprogressive in 17/20 patients, but two developed high-grade NHL several years later and one showed progressive disease. Actuarial probability of survival at 5 years was 85%. Granular lymphocyte morphology was relatively homogeneous, and peripheral blood counts were preserved in the most patients. Bone marrow lymphocytic infiltration was low, as assessed by bone marrow aspiration and/or biopsy. Eosinophilia was an outstanding feature in eight cases. Ultrastructurally, all cases showed parallel tubular arrays; cytoplasmic granules and numerous short microvilli were noticed. The lymphoid phenotype was heterogeneous, the most common being CD2+CD3+CD4-CD8+, but six patients (30%) were CD4+ with variable expression of natural killer-associated antigens. Chromosomal analysis was abnormal in 4/10 patients [trisomy 19, t(5;6); inv(14) and inv(10)]. The study of beta-chain of the T-cell receptor revealed clonal rearrangements in 14 (78%), restricted to CD3+ patients (92%). In vitro culture of myeloid precursors showed decreased CFU-GM in 5/6 patients. Virological studies for HTLV-I and II were negative. In conclusion, the presence of a clonal proliferation was not correlated with the clinical course or an associated disease.
 ...
PMID:Granular lymphocyte proliferative disorders: a multicenter study of 20 cases. 791 27

The incidence of trisomy 12 and p53 deletion was studied in a group of chronic B-lymphocytic leukemia (B-CLL) patients, using fluorescence in situ hybridization (FISH). Trisomy 12 was detected in eight of 50 patients (16%) and p53 deletion in six of 38 cases analyzed (15.8%). A statistically significant difference was observed between the incidence of trisomy 12 in patients with typical and atypical morphology (3.03% versus 41.18%). No correlation was found between this alteration and the rest of the clinical and biological parameters studied (adenopathies, hepatomegaly, splenomegaly, lymphocyte count, staging, CD11c expression, and resistance to chemotherapy). The p53 deletion was correlated with the presence of hepatomegaly and splenomegaly, advanced stage of disease, and resistance to conventional chemotherapy. The application of FISH to whole blood cell nuclei, without prior manipulation or culture, showed a higher percentage of cells with trisomy 12 than when the method was used following culture. We conclude that 1) FISH is a simple and sensitive technique for the detection of numerical and structural chromosome abnormalities; 2) Its application to uncultured samples obviates the alteration of results originated by the probable growth advantage of the normal or neoplastic cell population in vitro; 3) Trisomy 12 appears to define a B-CLL subgroup of atypical morphology; and 4) The p53 deletion is correlated with advanced stage of disease and resistance to treatment.
 ...
PMID:Trisomy 12 and p53 deletion in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: association with morphology and resistance to conventional chemotherapy. 883 Jul 19

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


1 2 Next >>