RESUMO
The factor H (FH) protein (also known as beta1H globulin) is the main regulator of the complement alternative pathway. It exhibits multivalent binding sites to the complement component C3b, and polyanions and one binding site to sialic acid and cell surfaces. These multiple binding sites confer to FH a decay-accelerating factor activity in the fluid phase as well as at the cell surface. A defect in FH activity or a FH protein deficiency triggers chronic inflammation and tissue injury, leading to various disorders impacting the kidney or the eye. In contrast, some pathogens, as well as cancer cells, develop various strategies to bind FH and thereby subvert a complement attack. We focus on the functions of FH, and review the main pathological conditions in which FH is involved. Since the pathogenesis is elusive, appropriate FH dosage in biological fluids and FH gene analysis may help in improving understanding of such diseases.
Assuntos
Fator H do Complemento/fisiologia , Animais , Artrite Reumatoide/imunologia , Ativação do Complemento , Fator H do Complemento/análise , Fator H do Complemento/genética , Humanos , Infecções/imunologia , Inflamação/imunologia , Nefropatias/imunologia , Neoplasias/imunologiaRESUMO
The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.
Assuntos
Leucemia-Linfoma de Células T do Adulto/metabolismo , Proteínas do Leite , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Sequência de Aminoácidos , Animais , Sequência de Bases , Biopolímeros , Divisão Celular , Linhagem Celular , Pré-Escolar , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática , Humanos , Interleucina-3/fisiologia , Janus Quinase 2 , Leucemia-Linfoma de Células T do Adulto/genética , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas de Fusão Oncogênica/química , Proteínas de Fusão Oncogênica/genética , Fosforilação , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-ets , Fator de Transcrição STAT5 , Transdução de Sinais , Transativadores/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
OBJECTIVES: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LNs) in men. METHODS: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of LN aged 18-75 years. During the same period, controls of the same age and sex as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPSs) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (ORs) and 95% CI were estimated using unconditional logistic regressions. RESULTS: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR = 8.4 (2.2 to 32.4), 10.8 (2.4 to 48.1), respectively). Exposure to insecticides, fungicides and herbicides were linked to a threefold increase in MM risk (OR = 2.8 (1.2 to 6.5), 3.2 (1.4 to 7.2), 2.9 (1.3 to 6.5)). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR = 4.9 (1.1 to 21.2), 4.1 (1.1 to 15.5), 5.1 (1.4 to 19.3)), although based on small numbers. Lastly, despite the increased ORs for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. CONCLUSIONS: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.
Assuntos
Leucemia de Células Pilosas/epidemiologia , Linfoma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/toxicidade , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Emprego/estatística & dados numéricos , França/epidemiologia , Fungicidas Industriais/toxicidade , Herbicidas/toxicidade , Doença de Hodgkin/induzido quimicamente , Doença de Hodgkin/epidemiologia , Humanos , Inseticidas/toxicidade , Leucemia de Células Pilosas/induzido quimicamente , Linfoma/induzido quimicamente , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/induzido quimicamente , Mieloma Múltiplo/epidemiologia , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto JovemRESUMO
We report a case of microsporidiosis in a 72-year-old woman presenting with prolymphocytic leukemia. The underlying conditions 7 months after leukemia was diagnosed were pancytopenia and immunosuppression due to alemtuzumab and pentostatin. The patient's status had worsened and she presented with dysuria. Urine cultures for bacteria were repeatedly negative. She was first empirically treated with broad-spectrum antibiotics. Three months later, urinary symptoms were persisting. Her blood lymphocyte count was 90/microl. Urine examination was positive for microsporidia using modified trichrome staining and Uvitex 2B fluorescence. Microsporidia were also detected in stools. The patient was cured by albendazole. This was consistent with an infection due to Encephalitozoon sp. Concurrently, disseminated toxoplasmosis was diagnosed. Toxoplasma gondii was detected in bone marrow, broncho-alveolar lavage and cerebrospinal fluid. She was successfully treated with sulfadiazine-pyrimethamine. Four cases of microsporidiosis in myeloid leukemic patients have been already described. The present case in a patient with lymphoid leukemia is the first to be reported.
Assuntos
Encefalitozoonose/complicações , Leucemia Prolinfocítica de Células T/complicações , Idoso , Albendazol/uso terapêutico , Animais , Medula Óssea/parasitologia , Encephalitozoon/isolamento & purificação , Encefalitozoonose/tratamento farmacológico , Fezes/microbiologia , Feminino , Humanos , Leucemia Prolinfocítica de Células T/microbiologia , Toxoplasma/isolamento & purificação , Toxoplasmose/complicações , Toxoplasmose/tratamento farmacológicoRESUMO
OBJECTIVE: To study potential role of smoking and alcohol in lymphoid neoplasms (LN). METHODS: A case-control study that included 824 cases and 752 hospital controls aged 18-75 years was conducted. Cases were newly diagnosed with non-Hodgkin's or Hodgkin's lymphoma, multiple myeloma, or lymphoproliferative syndrome (LPS). Controls were matched with the cases by gender, age, and center. RESULTS: Overall, smoking was not related to LN. However, average tobacco consumption tended to be inversely related to non-Hodgkin's lymphoma (NHL), LPS, and the hairy cell leukemia (HCL) subtype, with a significant negative trend for the latter (OR of 0.4, 0.2, 0.1 for consumptions of
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Doença de Hodgkin/epidemiologia , Linfoma não Hodgkin/epidemiologia , Mieloma Múltiplo/epidemiologia , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , França/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemAssuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Coagulantes/efeitos adversos , Fator VIIa/efeitos adversos , Deficiência do Fator XIII/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Trombose/tratamento farmacológico , Idoso , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Feminino , Humanos , Proteínas Recombinantes/efeitos adversos , Rituximab , Trombose/induzido quimicamente , Resultado do TratamentoRESUMO
One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Heterogeneidade Genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Translocação Genética , Adulto , Idoso , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 4 , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Vincristina/administração & dosagem , Microglobulina beta-2/sangueRESUMO
BACKGROUND: Congenital cutaneous leukaemia is rare. PATIENTS AND METHODS: A two-month-old girl presented bluish cutaneous macules of the trunk, histological examination of which suggested acute myeloid leukaemia (LAM B 5). The blood picture was negative for circulating tumour cells and the outcome under chemotherapy was favourable at one year of follow-up. DISCUSSION: The prognosis of congenital leukaemia is serious. Aleukaemic congenital leukaemia is seen occasionally but is rare. The existence of multiple cutaneous tumours in newborn infants raises the possibility of TORCH infection and of other malignant tumours such as nephroblastoma or neuroblastoma.
Assuntos
Leucemia Mieloide/patologia , Infiltração Leucêmica , Pele/patologia , Feminino , Humanos , LactenteAssuntos
Neoplasias do Sistema Nervoso Central/patologia , Linfoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Quimioterapia Adjuvante , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Transplante de Células-Tronco , Resultado do TratamentoRESUMO
Based on their multifaceted functions, B cells participate in several pathological settings such as lymphoproliferative disorders, autoimmune diseases and graft rejection. B cell-ablative therapy has thus emerged as a mainstay in these diseases. A number of anti-B cell antibodies (Abs) have been generated, among which anti-CD20 Abs appear to be efficient. Rituximab (RTX) is one of these anti-CD20 monoclonal Abs. Originally approved for the treatment of non-Hodgkin lymphoma, RTX is now being administered in other malignant proliferations, applied to an increasing number of autoimmune diseases and required to prevent rejection of a graft. Although this medication is remarkably safe, a handful of laboratory tests have been proposed to monitor RTX-treated patients. The efficacy in different diseases, and the emergence of new anti-CD20 Abs raise many questions. Thus, their detailed understanding can lead to a better issue for inhibition of immune responses.
Assuntos
Doenças Autoimunes/terapia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Rejeição de Enxerto/terapia , Imunoterapia/métodos , Neoplasias/terapia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Humanos , RituximabRESUMO
The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) in patients with newly diagnosed PCNSL. Twenty-five patients received two courses of initial chemotherapy combining methotrexate, etoposide, carmustine and methylprednisolone, and one course of ifosfamide-cytarabine followed by peripheral stem cell collection. Seventeen responsive patients then received HDT using carmustine, etoposide, cytarabine and melphalan with autologous stem cell rescue. After ASCT for responding patients or after salvage therapy for non-responders, whole brain radiation therapy at a dose of 30 Gy was delivered. The objective response rate to the induction chemotherapy was 84%. Four of the 21 responding patients did not have ASCT because of toxicity or refusal. With a median follow-up time of 34 months, the projected event free survival rate is 46% at 4 years. Projected overall survival is 64% at 4 years. Sixteen patients are actually in continuous complete response. No evidence of late treatment-related toxicity was observed. This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Transplante de Células-Tronco , Adulto , Carmustina/administração & dosagem , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Linfoma/mortalidade , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Transplante de Células-Tronco/mortalidade , Transplante AutólogoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Humanos , Lenalidomida , Prednisona/administração & dosagem , Recidiva , Indução de Remissão , Talidomida/administração & dosagem , Transplante AutólogoRESUMO
A total of 40 patients with B-CLL were investigated for CD5-triggered apoptosis and categorized as 20 resistant (group I) and 20 sensitive patients (group II). The densities of surface IgM (sIgM) and CD5 were lower in group I than group II, as were the percentages of CD79b+, CD38+, and Zap70-expressing B cells. CD5 signaling was mediated through the BCR in group II B cells, as established by coimmunoprecipitation of CD5 and CD79a and tyrosine phosphorylation of CD79a. Following colocalization of CD5 and sIgM in membrane lipid rafts (LRs), Syk became associated with these molecules, whereas SHP-1 was uncoupled from CD5. Nonresponsiveness to CD5 cross-linking in group I was ascribed to three possible abnormalities, and defined as three subgroups of patients. In subgroups Ia and Ib, CD5 and sIgM colocalized within the LRs. SHP-1 remained attached to the BCR in subgroup Ia, but not in subgroup Ib, where signal transduction was associated with an excess of truncated CD79b. In subgroup Ic, CD5 and sIgM segregated into different LRs, resulting in no signaling of apoptosis.
Assuntos
Linfócitos B/imunologia , Antígenos CD5/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Microdomínios da Membrana/fisiologia , Receptores de Antígenos de Linfócitos B/fisiologia , Antígenos CD/genética , Antígenos CD/imunologia , Apoptose , Antígenos CD79 , Técnicas de Cultura de Células , Citometria de Fluxo , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Transcrição GênicaRESUMO
PURPOSE: A prospective, multicenter, open-label, phase II clinical trial to assess oral fludarabine phosphate treatment in terms of safety, efficacy, and quality of life. Reference to a historical group of patients treated with the intravenous (IV) formulation allowed the two formulations to be compared. PATIENTS AND METHODS: Patients with previously untreated B-cell chronic lymphocytic leukemia received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. Efficacy was assessed using International Workshop on Chronic Lymphocytic Leukemia and National Cancer Institute criteria for response. Safety monitoring included WHO toxicity grading for adverse events. Quality of life was also assessed. RESULTS: Eighty-one patients received treatment. According to International Workshop on Chronic Lymphocytic Leukemia criteria, the overall response rate was 71.6% (complete remission, 37.0%; partial remission, 34.6%). The response rate using National Cancer Institute criteria was 80.2% (complete remission, 12.3%; partial remission, 67.9%). Median time to progression was 841 days (range, 28 to 1,146 days). The most frequently reported grade 3/4 toxicity was myelosuppression. WHO grade 3/4 hematological toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). Gastrointestinal toxicity was more common with the oral formulation than with IV fludarabine phosphate, but was generally mild to moderate and did not require treatment. Statistically significant improvements in mean emotional and insomnia quality-of-life scores were seen after treatment. CONCLUSION: This study demonstrates that oral fludarabine phosphate is clinically effective and generally well tolerated by patients with previously untreated B-cell chronic lymphocytic leukemia. Oral fludarabine phosphate has a similar clinical efficacy and safety profile to the IV formulation. Oral fludarabine phosphate does not adversely affect quality of life and may improve emotional and insomnia scores.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Fosfato de Vidarabina/análogos & derivados , Fosfato de Vidarabina/uso terapêutico , Administração Oral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Estudos Retrospectivos , Segurança , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Lactente , Recém-Nascido , Masculino , Metotrexato/administração & dosagem , Neutropenia/prevenção & controle , Prednisona/administração & dosagem , Proteínas Recombinantes , Trombocitopenia/prevenção & controle , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
This report describes the effects of cryopreservation on the adherent layer of human long-term bone marrow cultures (HLTBMC). Stromal cells are believed to be the most important cells of medullar microenvironment to regulate hematopoiesis. To study effects of cryopreservation, we compared the cell phenotypes of adherent layers of fresh and frozen-thawed bone marrows. To characterize stromal cells we used monoclonal antibodies reacting with components of these cells (CGA-7 alpha SM and gamma SM actin isoforms; HHF-35, all muscle actin isoforms; BMS-1, stromal cell lysosomes). The other components studied were: fibronectin (BMS-2 monoclonal antibody) and hematopoietic cells (monoclonal antibodies against CD45, CD33, and CD14). Results show a decrease of cells positive for CGA-7, HHF-35, and BMS-1, in adherent layer of HLTBMC of frozen-thawed bone marrows. Expression of BMS-2 is unchanged, and CD45 and CD14-positive cells proportionately increased. These results are consistent with an impairment of stromal cell proliferation in frozen-thawed marrows, without impairment of most stromal cell functions. The difference between stromal cell and hematopoietic cell kinetics seems to be an additional fact suggesting a different origin for both cell populations.
Assuntos
Medula Óssea/química , Células-Tronco Hematopoéticas/química , Actinas/análise , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Adesão Celular , Células Cultivadas/química , Criopreservação , Fibronectinas/análise , Antígenos de Histocompatibilidade/análise , Humanos , Antígenos Comuns de Leucócito , Receptores de Lipopolissacarídeos , Proteínas Musculares/análise , Fenótipo , Lectina 3 Semelhante a Ig de Ligação ao Ácido SiálicoRESUMO
Donor leukocyte infusions (DLI) have turned out to be an efficient way to re-establish complete remission (CR) in chronic myeloid leukemia (CML) patients relapsing after allogeneic bone marrow transplantation (BMT). In these patients, absence of PCR bcr-abl fusion transcripts confirmed the potency of donor leukocytes to induce molecular response in relapsed CML. This ensured sustained remission and long-term survival. In this study, the capacity of DLI to induce molecular remission in acute leukemia relapse after BMT was analyzed. The results showed that following DLI, leukemic cell eradication gradually occurred over a prolonged time period. The time to complete disappearance of the molecular marker of the disease was 30 weeks in RT-PCR analysis. A sustained and persistent elimination of an AML1/ETO-positive leukemic clone in an AML-M2 patient was observed. In contrast, an AML-M5 with t(11;19) and an E2A/PBX1-positive ALL achieving cytogenetic and molecular bone marrow CR developed following DLI unusual sites of extramedullary leukemia relapse, despite continued bone marrow remission. This study adds further proof of the benefit of donor cell therapy in acute leukemia but shows that complete leukemic cell eradication appears to require a critical interval in order to establish effective immune responses at all sites where leukemic cells persist.
Assuntos
Leucemia de Células B/terapia , Leucemia Mieloide Aguda/terapia , Transfusão de Leucócitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Infiltração Leucêmica , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A wide variety of abnormalities of the short arm of chromosome 12 has been reported in hematologic malignancies. The most frequent rearrangements result from t(12;21)(p13;q22) of childhood acute lymphoblastic leukemia, a translocation cryptic when leukemic cells are analyzed with chromosome banding techniques. This translocation results in a fusion of the TEL/ETV6 and AML1 genes. In this report, examples of rearrangements of 12p are presented. Study of two complex chromosome abnormalities associated with t(12;21) emphasizes the importance of using FISH in detection of such translocations. Three novel translocations involving the TEL/ETV6 gene localized on 12p13 are also reported: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). Finally, the presentation of two translocations with breakpoints located centromeric to TEL/ETV6 highlights the not uncommon involvement of genes other than TEL/ETV6 on 12p.
Assuntos
Anemia Refratária com Excesso de Blastos/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 12 , Proteínas de Ligação a DNA/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Adolescente , Criança , Pré-Escolar , Transtornos Cromossômicos , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 9 , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteínas Proto-Oncogênicas c-ets , Translocação Genética , Cromossomo X , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Although B chronic lymphocytic leukemia (B-CLL) is characterized by prolonged survival of CD5(+) B cells in vivo, these cells apoptose spontaneously in vitro. The effect of CD5 ligation on apoptosis was studied in 27 newly diagnosed patients with B-CLL, in relation to the expression of surface IgM (sIgM), CD79b, CD38, CD72 and CD19. B cells from 15 patients (group I) were resistant to anti-CD5-induced apoptosis, whereas apoptosis above spontaneous levels was seen in the remaining 12 studied (group II). Group II was then subdivided on the basis of differences in the time required to reach maximum apoptosis: whilst B cells from seven patients underwent apoptosis by 18 h, those from the remaining five needed 36 h to apoptose. The expression of sIgM, CD5, CD79b and CD38 was higher in group II than group I, suggesting that signaling for apoptosis might operate via CD79, and that CD38 expression was required. As shown by flow cytometry and confirmed by Western blotting, apoptosis was associated with a decrease in the ratios of Bcl-2/Bax and Bcl(XL)/Bax, due to an increase in the level of Bax, but no change in that of Bcl-2. This heterogeneous apoptotic response to CD5 ligation offers an explanation for the incomplete success of anti-CD5 monoclonal therapy, and might help identify patients who would respond to such treatment.