Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 60-year-old part Aboriginal woman was observed to develop severe neutropenia and a large granular lymphocyte (LGL) proliferation five years after the diagnosis of systemic lupus erythematosus (SLE). Monoclonality of the CD3+, CD4-, CD8+ LGL population was confirmed using the novel approach of X-linked restriction fragment length polymorphism (RFLP) analysis. Indeterminate HTLV-I serology was present. The patient responded to steroid therapy. LGL proliferation in the setting of SLE and the use of X-linked RFLP analysis to define LGL clonality have not previously been reported.
 ...
PMID:Monoclonal large granular lymphocyte proliferation in SLE with HTLV-I seroreactivity. 158 Aug 66

In this short review we discuss two clinical entities characterized by the accumulation in the blood of mature lymphocytes bearing T-cell markers (formerly T-cell chronic lymphocytic leukemia or T-CLL). The lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the expansion of granular lymphocytes (GL). Clinically most patients have a benign clinical course, while some have neutropenia. The neoplastic or reactive nature of the disease is discussed. T-CLL with a T-helper phenotype is, on the other hand, an aggressive disease with poor survival. Patients may be classified into two subgroups according to the presence of serum antibodies against HTLV-I. The possible etiological role of HTLV-I in the disease is discussed.
 ...
PMID:Relevance of monoclonal antibody phenotyping and of genetic studies in the classification of T-cell leukemia/lymphoma. 295 37

LGL leukemia results from a chronic, clonal proliferation of LGL. Chronic neutropenia with recurrent bacterial infection and splenomegaly are common clinical manifestations. Rheumatoid arthritis coexists in some of these patients, who thus resemble patients with Felty syndrome. Other hematologic abnormalities that may occur include pure red-cell aplasia and adult-onset cyclic neutropenia. Lymphoid infiltration of bone marrow, splenic red pulp cords, and hepatic sinusoids is characteristic; lymph node and skin involvement are rare. Multiple serologic abnormalities are frequently present, including positive tests for rheumatoid factor and/or antinuclear antibody, polyclonal hypergammaglobulinemia, and circulating immune complexes. Antineutrophil and antiplatelet antibodies are often present. Leukemic LGL exhibit phenotypic heterogeneity; the most common phenotype in our patients is CD2+, CD3+, CD8+, HNK-1+, CD16-. Despite markedly increased numbers of LGL, functional activity of the cells is usually decreased. The mechanism of cytopenias is uncertain: in pure red-cell aplasia, it appears to be due to suppressive effect on erythropoiesis by abnormal LGL, but in patients with chronic neutropenia it may be antibody-mediated. Although most patients appear to have a relatively benign clinical course, mortality from infections and progressive lymphoproliferation is substantial. Optimal therapy remains undefined. Some preliminary evidence suggests that LGL leukemia may be associated with infection with a retrovirus similar to HTLV-I. Although relatively rare, LGL leukemia is of interest because a better understanding of this disease process may contribute to our knowledge of autoimmune diseases, the immunoregulatory functions of LGL, and the mechanisms controlling normal hematopoiesis.
 ...
PMID:Large granular lymphocyte leukemia. Report of 38 cases and review of the literature. 362 48

A 52-year-old man, who complained of tarry stool and systemic lymphadenopathy, was admitted to our hospital on July 2, 1992. Biopsy showed diffuse large cell lymphoma. Leukocytosis with atypical lymphocytes was not shown in the peripheral blood, but there was an elevated serum LDH level. The man was found to have both HTLV-I antibody and the monoclonal integration of proviral DNA in malignant lymph node cells obtained at biopsy. The diagnosis was lymphoma-type adult T-cell leukemia (ATLL). The chemotherapy regimens of MI-FP, CHOP and modified DHAP were used for the treatment, but were not effective. So, he was treated with etoposide 75 mg orally for 25 days (chronic oral etoposide therapy) and achieved partial remission. This chemotherapy induced myelosuppression with neutropenia, but there was no documented infection. Chronic oral etoposide therapy is an effective regimen for patients with relapse or refractory lymphoma.
 ...
PMID:[Adult T cell leukemia/lymphoma effectively treated with chronic oral etoposide]. 837 79

Ten HTLV-I-associated myelopathy (HAM) patients (four men and six women aged 38 to 58 years) with Expanded Disability Status Scale (EDSS) scores ranging from 4.0 to 8.5 entered an open-label zidovudine study. A high-dosage induction (2 g/d for 4 weeks) was followed by 1 g/d for 20 weeks. Five patients were natives of the Caribbean island Hispaniola, and one each was from Colombia, Cuba, El Salvador, Jamaica, and the United States; all were positive by polymerase chain reaction, and nine had positive Western immunoblots for HTLV-I. Side effects included anxiety, insomnia, gastric upset, anorexia, and loss of taste. Preexisting leg cramps were increased in two and headaches in one. Hemoglobin decreased from a mean of 13.5 to 11.8 g/dl and the hematocrit from 40.7% to 34.9% at 8 weeks, and then stabilized. Neutropenia appeared regularly but did not necessitate drug withdrawal. Mean EDSS scores changed little for the group as a whole, but the seven ambulatory patients improved objectively, with their scores dropping from 5.5 to 4.0 and none worsening. Timed gait improved by at least 50%. Following withdrawal, four of the five who had improved regressed. Zidovudine appears to be safe in subjects with HAM who have no other major health problems and should be investigated further.
 ...
PMID:High-dose zidovudine induction in HTLV-I-associated myelopathy: safety and possible efficacy. 841 77

We report on an HTLV-I carrier showing clonal proliferation of gammadelta-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/microl with 89% lymphocytes. The proliferating gammadelta-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCRdelta1, and HLA-DR but negative for CD4, CD8, and deltaTCS1. Clonally rearranged TCRgamma-chain (Jgamma) and TCRbeta-chain (Cbeta1) genes were detected by Southern blot analysis. Clonality of these proliferating gammadelta-T cells was confirmed by CDR3 size analysis for the TCRdelta-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral DNA was detected by PCR analysis, but clonal integration of HTLV-I proviral DNA was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCRalphabeta+ type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation.
 ...
PMID:Clonal expansion of gammadelta-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis. 1008 29

Clonal diseases of large granular lymphocyte (LGL) disorders can arise from a CD3+ T-cell lineage or from a CD3- NK-cell lineage. CD3+ LGL leukemia is the most frequent form of LGL leukemia. T-LGL leukemia usually affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chonic neutropenia, anemia, and rheumatoid arthrititis are the main clinical manifestations. The most common phenotype is CD3+, alphabeta+, CD8+, CD57+. Clonality is detected by clonal rearrangement of the T-cell receptor gene. NK-cell LGL proliferative disorders include NK LGL leukemia which is a very aggressive disease and NK chronic lymphocytosis. Serologic findings show frequent reactivity to the BA21 epitope of HTLV-I env p21e, suggesting that a cellular or retroviral protein with homology to BA21 may be important in pathogenesis of these diseases. Clonal expansion may be facilitated by IL12 and IL15 cytokines expressed by leukemic LGL, and also by a defective Fas (CD95) apoptotic pathway. Leukemic LGL constitutively express Fas and Fas-Ligand but they are resistant to Fas-induced apotosis. Neutropenia could be due to soluble Fas-Ligand which is highly secreted in the patient's sera. Clinical and molecular remission can be obtained with oral low-dose methotrexate. Leukemic LGL express a multi-drug resistance phenotype (PgP+/LRP+) that could partly explain the chemoresistance observed in aggressive cases. It is suggested that LGL leukemia can serve as a useful model of dysregulated apoptosis as an underlying mechanism for both malignancy and autoimmune disease.
 ...
PMID:Current concepts: large granular lymphocyte leukemia. 1074 98

BACKGROUND: Clonal diseases of large granular lymphocyte (LGL) disorders can arise from a CD3+ T-cell lineage or from a CD3- NK-cell lineage. CD3+ LGL leukemia is the most frequent form of LGL leukemia and is a distinct entity by FAB and REAL classifications. METHODS: The clinical course, biological features, and recent data on pathogenesis of CD3+ LGL leukemia are reviewed. The spectrum of differential diagnosis is described. RESULTS: T-LGL leukemia affects elderly people. Approximately 60% of patients are symptomatic; recurrent infections secondary to chronic neutropenia, anemia, and rheumatoid arthritis are the main clinical features. The most common phenotype is CD3+, CD8+, CD57+. Clonality is detected by clonal rearrangement of the T-cell receptor gene. Clinical and molecular remission can be obtained with oral low-dose methotrexate. Serologic findings show frequent reactivity to the BA21 epitope of HTLV-I env p21e, suggesting that a cellular or retroviral protein with homology to BA21 may be important in pathogenesis. Clonal expansion may be facilitated by IL-12 and IL-15 lymphokines. Constitutive expression of Fas ligand by leukemic LGLs support the hypothesis that leukemic cells arise from antigen-activated cytotoxic T cells. Leukemic LGLs express a multidrug-resistance phenotype that could partly explain the chemoresistance observed in aggressive cases. CONCLUSIONS: CD3+ LGL leukemia is a distinct lymphoproliferative T-cell disorder with specific clinicobiological aspects. The clinical spectrum of LGL proliferations is wide and immunophenotypic, and genotypic studies are needed to establish the diagnosis.
 ...
PMID:Large Granular Lymphocyte Leukemia. 1076 Oct 14