Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two middle-aged patients with T cell lymphoma, both natives of Bucharest, Romania, tested positive for HTLV-I antibodies. Malignant cells had the typical phenotype and morphology of adult T cell leukemia/lymphoma (ATL). Both cases presented with extranodal manifestation, hypercalcemia, early recurrence after initial responses to therapy, and subsequent resistance to conventional and intensified chemotherapy. Infection with HTLV-I was confirmed by PCR analyses of serial biopsies. Neither patient reported known risk factors for HTLV-I infection. This report points to the possibility that Romania may represent an endemic area for HTLV-I and should heighten the awareness towards HTLV-I infections in Romanian patients.
Leukemia 1996 Aug
PMID:HTLV-I-associated adult T cell leukemia/lymphoma in two patients from Bucharest, Romania. 870 46

We studied 276 fever episodes with an absolute neutrophil count (ANC) < 500/mm3 to determine patient characteristics predicting serious infection. Infections occurred in 38% of patients. Blood cultures were positive in 58% of documented infections. There was no difference in the rates of infection or positive blood culture when ANC was < 200/mm3 compared with a higher ANC. However, certain high risk infections were more common with an ANC < 200/ mm3. Leukemia patients had more infections compared with other groups. Serious infections were more common during induction therapy or relapse. Infection incidence varied significantly with patient age and onset of fever in the inpatients. Less than one fifth of febrile neutropenic episodes had no risk features for serious infection. We conclude that several clinical characteristics correlate with serious infection in febrile, neutropenic children and adolescents receiving modern supportive care. Despite improvements in supportive care measures, most febrile, neutropenic patients need close observation and empiric intravenous antibiotic therapy.
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PMID:Infection risk factors in febrile, neutropenic children and adolescents. 873 37

Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high incidence in the southwestern region. The retrovirus, human T-lymphotropic virus type I (HTLV-I), is the causative agent of ATL. In ATL-endemic areas, the rate of HTLV-I carriers is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumor cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes: acute, chronic, smoldering, and lymphoma type. Chemotherapy is not effective; the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, from man to female, or by blood transfusion. Infection with HTLV-I can lead to other diseases, including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I uveitis.
Leukemia 1997 Apr
PMID:Kenneth MacGredie Memorial Lectureship. Adult T-cell leukemia/lymphoma. 920 96

Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against AIDS. Two experimental FIV vaccines have been developed: one consisting of fixed infected cells and the other of inactivated whole virus. Both vaccines elicited strong CTL responses to FIV and high virus neutralizing (VN) antibody titers. Over 90% of vaccinated cats were protected against intraperitoneal infection with 10 cat infectious dose 50% (10 CID50) of either homologous FIVPet or heterologous FIVDix. As a means to evaluate the mechanism of vaccine protection, cats were either passively immunized with serum antibodies or transfused with peripheral blood cells from FIV-vaccinated cats. Cats passively immunized with vaccine sera or purified vaccine antibodies were protected from homologous FIV infection at a challenge doses which infected all control cats (5 and 10 CID50). Such passive protection was not achieved against heterologous FIV challenge. More importantly, cats transfused with washed blood cells from half-matched vaccinated cat were protected from FIV challenge (20 and 50 CID50). As expected, protection was not observed in cats transfused with cells from either unmatched vaccinated or half-matched unvaccinated cats. Further, only peripheral-blood cells from vaccinated cats had FIV-specific CTL responses to both autologous and half-matched target cells. Overall, these findings suggest that both humoral and cellular immunity are required for optimal vaccine protection.
Leukemia 1997 Apr
PMID:Mechanism(s) of FIV vaccine protection. 920 11

Human T cell leukemia virus type I (HTLV-I) or its transcriptional transactivator, Tax1, was introduced into a human osteosarcoma cell line, HOS, and a Moloney murine sarcoma virus-positive HOS cell line, S+L-HOS. These HTLV-I- or Tax1-expressing cells were injected subcutaneously into nude mice to investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not form any tumors even in the presence of HTLV-I or Tax1. S+L-HOS cells did form small tumors in two-thirds of nude mice. Infection of S+L-HOS cells with HTLV-I, or transduction of Tax1 into S+L-HOS cells markedly facilitated the tumor formation, and the tumor-bearing mice showed marked splenomegaly and neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF) were detected in sera of these mice and also in the culture supernatants of Tax1-expressing human cells, suggesting that G-CSF in the mouse sera was produced by the human cells. In sera of some mice with splenomegaly and neutrophilia, high levels of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) were observed, suggesting that Tax1 produced by human cells induced mouse cells to produce mGM-CSF. Only S+L-HOS cell lines expressing Tax1 showed high tumorigenicity in nude mice. Thus, this system will be a useful model of tumor formation, splenomegaly and neutrophilia dependent on Tax1.
Leukemia 2000 Aug
PMID:Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1. 1094 44

The effectiveness of intensive post-remission chemotherapy regimens for adult patients with acute lymphoblastic leukemia (ALL) is limited by both a high rate of disease recurrence and a substantial incidence of treatment toxicity. To evaluate a potentially more effective and less toxic approach, we conducted a multicenter phase III trial of consolidation therapies comparing the standard L10M regimen with one combining the brief, intensive L17M regimen and escalating methotrexate (MTX) and L-asparaginase (L-asp). Patients over age 15 with previously untreated ALL were eligible. Induction therapy included vincristine, prednisone, doxorubicin, cyclophosphamide and intrathecal methotrexate administered over 36 days. Patients who achieved complete remission (CR) were randomized to receive consolidation with either the L10M regimen or with DAT (daunomycin, cytosine arabinoside, 6-thioguanine) and escalating MTX and L-asp. The randomization was stratified by age, WBC and Ph chromosome status. Maintenance therapy was the same in both arms. Of 353 eligible patients, 218 (62%) achieved CR and 195 were randomized. The treatment arms did not differ significantly with respect to disease-free survival (DFS; P= 0.46) or overall survival (P= 0.39). Estimated DFS at 5 years was 32% (95% confidence interval (CI) 23-42%) in the L10M arm and 25% (95% CI 16-33%) in the DAT/MTX/L-asp arm. In each arm, 4% of patients died of toxicities (infection in all but one case). Infections and nausea/vomiting were somewhat more common in the L10M arm (occurring in 68% and 53% of patients respectively) than the DAT/MTX/L-asp arm (56% and 33%). The DAT/MTX/L-asp consolidation regimen was associated with some reduction in nonfatal toxicities, but no significant improvement in DFS, overall survival or non-relapse mortality when compared to the standard L10M regimen.
Leukemia 2001 Feb
PMID:Comparison of the L10M consolidation regimen to an alternative regimen including escalating methotrexate/L-asparaginase for adult acute lymphoblastic leukemia: a Southwest Oncology Group Study. 1123 36

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down-regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis.
Leukemia 2001 Mar
PMID:Using death to one's advantage: HIV modulation of apoptosis. 1123 54

Purified, high-titer adenovirus encoding murine CD154 (Ad-CD154) or human CD154 (Ad-hCD154) was used to infect lymph node cells isolated from patients with follicle center lymphoma. Infection of lymphoma B cells with Ad-CD154 at a multiplicity of infection (MOI) ratio of 100 or higher resulted in high-level transgene expression. Additionally, upon infection of lymphoma B cells, only Ad-CD154 resulted in surface expression of CD154, despite similar, high-level expression of either human or mouse CD154 by HeLa cells infected with Ad-hCD154 or Ad-CD154, respectively. Moreover, infection of lymphoma B cells with Ad-CD154, but not Ad-hCD154 or adenovirus encoding Eschericheria coli beta-galactosidase (Ad-LacZ), induced the neoplastic B cells to express higher levels of immune co-stimulatory molecules that are required for proficient presentation of antigen to T cells. Consistent with this, we found that Ad-CD154 infected lymphoma B cells could stimulate T cells to proliferate or produce interferon-gamma in allogeneic or autologous mixed lymphocyte interactions. We conclude that lymphoma B cells can be infected with Ad-CD154 and that this significantly enhances their recognition by allogeneic or autologous T cells. As such, Ad-CD154-transduced lymphoma B cells may have potential for the active immune therapy of patients with follicle center lymphoma.
Leukemia 2001 Sep
PMID:T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154. 1151 7

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation.
Leukemia 2001 Oct
PMID:Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia. 1158 7

We describe here the development of a murine system for the identification of genes involved in myelomonocytic neoplasms. Transgenic C57BL/6J mice expressing SV40 early region under a myelomonocytic promoter develop histiocytic sarcomas with a latency of 167 days. We used retroviral proviral tagging to accelerate tumorigenesis and to uncover genetic changes that contribute to tumor development. Infection of transgenic mice with Friend murine leukemia virus (F-MuLV) shortened the latency of morbidity to 103 days (P< 0.001); this was associated with clonal proviral integrations in tumor DNA. As expected for F-MuLV, proviral insertions occurred at Fli1 in both transgenic and nontransgenic tumors. Four insertions were found at a novel locus, termed Fim4, on chromosome 6. This region is syntenic to human 7q32, a region that is commonly deleted in human myelodysplastic syndrome and acute myeloid leukemia. A murine BAC containing Fim4 was sequenced and analyzed, and while there was significant human-mouse homology in the area of the insertions, no candidate gene has been identified. Thus we have established a system to identify genes involved in myelomonocytic tumors, and have used it to identify Fim4, a new common site of proviral insertion. Study of this locus may provide insight into genes involved in AML-associated 7q32 deletions in humans.
Leukemia 2002 Sep
PMID:F-MuLV acceleration of myelomonocytic tumorigenesis in SV40 large T antigen transgenic mice is accompanied by retroviral insertion at Fli1 and a novel locus, Fim4. 1220 Jun 99


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