RESUMEN
Correction to:Wien Klin Wochenschr 2018 https://doi.org/10.1007/s00508-018-1365-5 The original version of this article unfortunately contained a mistake. Table Nr. 1 was inconsistent. The corrected version of Table 1 is given below. We apologize for any inconveniences this may have .
RESUMEN
The oral Janus associated kinase (JAK1/2) inhibitor ruxolitinib has been available for treatment of patients with intermediate or high-risk myelofibrosis in Europe since 2012. Since its introduction, the expertise of prescribing doctors with respect to ruxolitinib function, efficacy and adverse effects has consistently been augmented, resulting in therapy modalities that are better tailored to individual patients as well as in increased safety of the treatment. The present consensus on ruxolitinib therapy management has been elaborated by Austrian experts in myeloproliferative neoplasms in line with international treatment guidelines. Our recommendations aim to contribute to an improved management of patients with myelofibrosis treated with ruxolitinib.
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Mielofibrosis Primaria , Pirazoles/uso terapéutico , Austria , Consenso , Europa (Continente) , Humanos , Nitrilos , Mielofibrosis Primaria/tratamiento farmacológico , Pirimidinas , Estudios RetrospectivosRESUMEN
The entity "myelofibrosis" represents a subgroup of the Philadelphia chromosome-negative myeloproliferative neoplasms. It comprises primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. This heterogeneous disease is characterized by clonal myeloproliferation, dysregulated kinase signalling and the abnormal expression of several proinflammatory cytokines. Clinically, patients present with symptoms related to thrombocytosis/leukocytosis, anemia and/or progressive splenomegaly. Mutations in Janus kinase 2, an enzyme that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 60% of patients with primary myelofibrosis. Recent molecular advances have not only elucidated critical pathways in the pathogenesis of the disease, but also contributed to a more precise assessment of a patient's individual risk. While allogeneic stem cell transplantation remains the only curative treatment, the natural course of the disease and the patient's survival and quality of life may be improved by new treatments, notably ruxolitinib, the first Janus kinase 1/2 inhibitor approved for the management of myelofibrosis. Additional treatment options are being explored.
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Anticuerpos Monoclonales/uso terapéutico , Testimonio de Experto , Hematología/normas , Terapia Molecular Dirigida/métodos , Guías de Práctica Clínica como Asunto , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/terapia , Austria , Mielofibrosis Primaria/patologíaRESUMEN
Relatively little is known about the long-term outcome of patients with Helicobacter pylori (HP)-negative gastric lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with antibiotic therapy as sole management. We have analyzed all patients with HP-negative gastric MALT lymphoma undergoing antibiotic therapy as sole management of their disease. HP negativity was defined as negative histology, breath test and serology, and response to treatment, survival and long-term outcome was assessed together with clinico-pathological characteristics including t(11; 18) (q21; q21) translocation. Out of 97 patients with gastric MALT lymphoma, 24 were HP-negative, and 13 (5 females and 8 males) underwent only antibiotic management for initial therapy. Eight had stage I and five were found to have stage II disease, with three patients suffering from an underlying autoimmune disease. Antibiotic therapy consisted of standard HP eradication regimens consisting of clarithromycin in all patients, along with metronidazole in seven and amoxicillin in six plus a proton-pump inhibitor. After a median follow-up of 95 months (42-, 181+), 12/13 patients are alive. Six patients with stage I disease achieved an objective response (five complete (CR) and one partial remission, 46 %), four had stable disease (lasting 11-27 months), and three progressed. All patients with stable disease received chemotherapy, but only one patient due to clear cut progression. One patient relapsed 23 months after initial CR, and achieved a second CR with antibiotics now lasting 87 months. These results indicate that a relevant percentage of patients with HP-negative gastric MALT lymphoma may benefit from antibiotic therapy and do not require additional oncological therapies. Our data suggest that the remissions seen in these patients might be durable as evidenced by prolonged follow-up in our series.
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Antibacterianos/uso terapéutico , Helicobacter pylori , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. MATERIAL AND METHODS: We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999-2012. Median age at diagnosis was 64 years (IQR 51-75) and follow-up time 43 months (IQR 16-92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. RESULTS: The majority of patients presented with stage IE (nâ=â40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9-39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (pâ=â0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. CONCLUSION: Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.
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Linfoma de Células B de la Zona Marginal/terapia , Neoplasias Orbitales/terapia , Anciano , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Orbitales/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion.
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Células Madre Hematopoyéticas/citología , Células del Estroma/citología , Células del Estroma/metabolismo , Animales , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Células Cultivadas , Humanos , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative rescue therapy for patients (pts) with chemotherapy-refractory acute leukaemia. Disease control prior to HSCT is essential for long-term disease-free survival after HSCT. PATIENTS AND METHODS: We have retrospectively analysed the outcome of 20 pts aged 21-64 years with refractory leukaemia (acute myeloid leukaemia, n = 16; acute lymphatic leukaemia, n = 4) who received debulking therapy with clofarabine (10 mg/m², days 1-4) and cyclophosphamide (200 mg/m², days 1-4; ClofCy) prior to HSCT. RESULTS: Clofarabine/cyclophosphamide (1-4 cycles) was well tolerated and resulted in a substantial reduction of leukaemic cells in all pts. HSCT was performed in 15 of 20 pts. After HSCT (myeloablative, n = 9; dose-reduced, n = 6), all pts showed engraftment and full donor chimerism (related donors, n = 4 or unrelated donors, n = 11) and all pts achieved complete haematologic remission (CR). The median survival after HSCT is 531 days (range: 48-1462 days), and six pts are still alive after a median of 1245 days. Seven pts died after they had relapsed between days +152 and +1496. One patient died from acute graft-versus-host disease (day +48) and one from systemic fungal infection (day +87). CONCLUSION: Clofarabine/cyclophosphamide is a novel effective treatment approach for pts with chemotherapy-refractory acute leukaemia prior to HSCT. Whether this novel debulking protocol leads to improved long-term outcome in pts with refractory leukaemias remains to be determined in forthcoming clinical studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Nucleótidos de Adenina/administración & dosificación , Adulto , Arabinonucleósidos/administración & dosificación , Clofarabina , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
We have performed a retrospective analysis of all patients with extragastric mucosa-associated lymphoid tissue (MALT) lymphoma treated at our institution to compare the efficacy of first-line therapeutic modalities including surgery, radiation, systemic therapy, and antibiotics. One hundred eighty-five patients with extragastric MALT lymphoma with a median age of 63 (interquartile range (IQR) 50-74) years and a median follow-up time of 49 (IQR 18-103) months were retrospectively analyzed. Time to progression and time to next therapy were used as surrogate endpoints for efficacy. Patients having either surgery (100 %), chemo/immunotherapy (85.5 %), or radiation (80 %) had significantly (p = 0.01) higher response rates than patients treated with antibiotics (33.3 %). Patients who were irradiated had significantly more progressive disease, but also the longest follow-up time. Stage, elevated LDH, anemia, elevated beta-2 microglobulin, plasmacytic differentiation, monoclonal gammopathy, or autoimmune disease did not influence the rate of disease progression nor did complete remission or partial remission from initial therapy influence time to and rate of progression. There was no significant difference in the median time to progression (p = 0.141), but the estimated time to progression (p = 0.023) as well as the estimated time to next therapy (p = 0.021) was significantly different among the various cohorts favoring surgery, chemo/immunotherapy, and radiation. Our results suggest extragastric MALT lymphoma as a potential systemic disease irrespective of initial stage. Radiation, surgery, and chemo/immunotherapy seem to be equally effective in achieving remissions and prolonged progression free survivals, but a curative potential is questionable. Localized MALT lymphomas affecting the thyroid gland or the lungs have excellent long-term progression-free survivals with surgical treatment only.
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Linfoma de Células B de la Zona Marginal/terapia , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Austria/epidemiología , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Terapia Combinada , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias del Ojo/sangre , Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/radioterapia , Neoplasias del Ojo/cirugía , Neoplasias del Ojo/terapia , Humanos , Inmunoterapia , Estimación de Kaplan-Meier , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Linfoma de Células B de la Zona Marginal/sangre , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma de Células B de la Zona Marginal/radioterapia , Linfoma de Células B de la Zona Marginal/cirugía , Persona de Mediana Edad , Especificidad de Órganos , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/sangre , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/radioterapia , Neoplasias de las Glándulas Salivales/cirugía , Neoplasias de las Glándulas Salivales/terapia , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/terapia , Resultado del TratamientoRESUMEN
Mouse haematopoietic stem cells (HSCs) undergo a postnatal transition in several properties, including a marked reduction in their self-renewal activity. We now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. Lentivirus-mediated overexpression of Lin28 in adult HSCs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of Hmga2, a well-established let-7 target that is upregulated in fetal HSCs. Conversely, HSCs from fetal Hmga2(-/-) mice do not exhibit the heightened self-renewal activity that is characteristic of wild-type fetal HSCs. Interestingly, overexpression of Hmga2 in adult HSCs does not mimic the ability of elevated Lin28 to activate a fetal lymphoid differentiation program. Thus, Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential.
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Proteínas de Unión al ADN/metabolismo , Proteína HMGA2/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , MicroARNs/metabolismo , Animales , Animales Recién Nacidos , Diferenciación Celular , Proliferación Celular , Feto , Citometría de Flujo , Regulación del Desarrollo de la Expresión Génica , Proteína HMGA2/genética , Linfocitos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Proteínas de Unión al ARN , Transducción de Señal , Regulación hacia ArribaRESUMEN
Invasive systemic fungal infections are a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation. We report the case of a fatal infection with Hormographiella aspergillata in a patient undergoing allogenic peripheral blood stem cell transplantation for acute myeloid leukaemia.
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Agaricales/aislamiento & purificación , Dermatomicosis/complicaciones , Dermatomicosis/diagnóstico , Leucemia Mieloide Aguda/complicaciones , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Dermatomicosis/microbiología , Dermatomicosis/patología , Resultado Fatal , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/terapia , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/patología , Persona de Mediana Edad , Trasplante Homólogo/efectos adversosRESUMEN
Accumulating evidence suggests that human cancers develop through a step-wise, but nonlinear process of cellular diversification and evolution. Recent mutational analyses indicate that this process is more complex and diverse than anticipated before whole-genome sequencing methods were readily available. Examples are also emerging now of genetically abnormal clones of cells that have acquired mutations with known oncogenic potential but, nevertheless, may show no manifestations of malignant change for many years. To accommodate these diverse realities, we suggest the term neoplastic refer to clones of cells that have any type of somatic aberrancy associated with an increased propensity to become malignant, and the derivative term neoplastic stem cell be adopted to identify the cells responsible for the long-term maintenance of such clones. Neoplastic clones would thus include those that never evolve further, as well as those that eventually give rise to fully malignant populations, and all stages in between. The term cancer stem cells would then be more appropriately restricted to cells generating subclones that have established malignant properties. More precise molecular understanding of the different stem cell states thus distinguished should contribute to the development of more effective prognostic and therapeutic tools for cancer diagnosis and treatment.
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Células Madre Neoplásicas/fisiología , Progresión de la Enfermedad , Epigénesis Genética , Humanos , Neoplasias/diagnóstico , Neoplasias/patología , Neoplasias/terapia , Lesiones Precancerosas/patologíaRESUMEN
The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.
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Células Madre Neoplásicas , Terminología como Asunto , Animales , Diferenciación Celular , Transformación Celular Neoplásica , Evolución Clonal , Humanos , Células Madre Neoplásicas/fisiologíaRESUMEN
Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other appears selectively lymphoid deficient. We now show that both of these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the rarer, lymphoid-deficient HSCs immediately gaining an increased representation in the fetal bone marrow, suggesting that the marrow niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis of HSC expansion posttransplant showed that both subtypes display an extensive but variable self-renewal activity with occasional interconversion. Clonal analysis of their differentiation programs demonstrated functional and molecular as well as quantitative HSC subtype-specific differences in the lymphoid progenitors they generate but an indistinguishable production of multipotent and myeloid-restricted progenitors. These findings establish a level of heterogeneity in HSC differentiation and expansion control that may have relevance to stem cell populations in other hierarchically organized tissues.
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Células Madre Hematopoyéticas/citología , Linfopoyesis , Animales , Diferenciación Celular , Linaje de la Célula , Senescencia Celular , Femenino , Citometría de Flujo , Humanos , Ratones , Ratones Endogámicos C57BL , EmbarazoRESUMEN
Heterogeneity in cell populations poses a major obstacle to understanding complex biological processes. Here we present a microfluidic platform containing thousands of nanoliter-scale chambers suitable for live-cell imaging studies of clonal cultures of nonadherent cells with precise control of the conditions, capabilities for in situ immunostaining and recovery of viable cells. We show that this platform mimics conventional cultures in reproducing the responses of various types of primitive mouse hematopoietic cells with retention of their functional properties, as demonstrated by subsequent in vitro and in vivo (transplantation) assays of recovered cells. The automated medium exchange of this system made it possible to define when Steel factor stimulation is first required by adult hematopoietic stem cells in vitro as the point of exit from quiescence. This technology will offer many new avenues to interrogate otherwise inaccessible mechanisms governing mammalian cell growth and fate decisions.
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Técnicas de Cultivo de Célula/métodos , Células Madre Hematopoyéticas/citología , Técnicas Analíticas Microfluídicas/métodos , Análisis de Matrices Tisulares , Adulto , Técnicas de Cultivo de Célula/instrumentación , Proliferación Celular , Ensayos Analíticos de Alto Rendimiento , Humanos , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
Although imatinib has become standard first-line therapy in chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is still considered to be an important treatment alternative for patients with drug resistance or advanced disease. We retrospectively analyzed 175 adult CML patients who underwent HSCT at our institution between 1983 and 2007, with the aim to compare outcomes in patient subgroups and to identify prognostic variables. The median follow-up was 65 months. The probability of overall survival (OS) for all patients was 62%, with a significant improvement seen in the imatinib-era (2001-2007) compared to previous time periods (P <.05). Furthermore, a significantly better outcome for patients with chronic phase CML compared to patients with accelerated or blast phase could be observed (P < .05). Cumulative incidence (CI) of treatment-related mortality (TRM) was 9.7% at 100 days and 1 year after HSCT. CI of relapse was 5% at 1 year and 7.5% at 3 years after HSCT. Post-HSCT outcome was not influenced by pretreatment therapy with imatinib, donor type, or a conditioning regimen with total body irradiation (TBI). These data confirm earlier observations and suggest that allogeneic HSCT is still an important treatment option for high-risk patients with CML, and should thus remain an integral component in current and future treatment algorithms.
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Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/tendencias , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adulto , Benzamidas , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Pronóstico , Pirimidinas/uso terapéutico , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
The use of the green fluorescent protein (GFP) to label specific cell types and track gene expression in animal models, such as mice, has evolved to become an essential tool in biological research. Transgenic animals expressing genes of interest linked to GFP, either as a fusion protein or transcribed from an internal ribosomal entry site (IRES) are widely used. Enhanced GFP (eGFP) is the most common form of GFP used for such applications. However, a red fluorescent protein (RFP) would be highly desirable for use in dual-labeling applications with GFP derived fluorescent proteins, and for deep in vivo imaging of tissues. Recently, a new generation of monomeric (m)RFPs, such as monomeric (m)Cherry, has been developed that are potentially useful experimentally. mCherry exhibits brighter fluorescence, matures more rapidly, has a higher tolerance for N-terminal fusion proteins, and is more photostable compared with its predecessor mRFP1. mRFP1 itself was the first true monomer derived from its ancestor DsRed, an obligate tetramer in vivo. Here, we report the successful generation of a transgenic mouse line expressing mCherry as a fluorescent marker, driven by the ubiquitin-C promoter. mCherry is expressed in almost all tissues analyzed including pre- and post-implantation stage embryos, and white blood cells. No expression was detected in erythrocytes and thrombocytes. Importantly, we did not encounter any changes in normal development, general physiology, or reproduction. mCherry is spectrally and genetically distinct from eGFP and, therefore, serves as an excellent red fluorescent marker alone or in combination with eGFP for labelling transgenic animals.
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Regulación de la Expresión Génica , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Animales , Perfilación de la Expresión Génica , Vectores Genéticos , Genotipo , Leucocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Regiones Promotoras Genéticas , Proteína Fluorescente RojaRESUMEN
BACKGROUND: The prognostic values of the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have widely been demonstrated in diffuse large B-cell lymphoma and follicular lymphoma. No attempts to assess their applicability in MALT lymphoma have been made so far. PATIENTS AND METHODS: A total of 143 patients with MALT-lymphoma were analysed. Parameters of both IPI and FLIPI were retrospectively assessed and correlated with relapse and time to relapse as markers of clinical course. RESULTS: According to IPI, 96 patients (67%) were classified as low, 22 (15%) low-intermediate, 17 (12%) high-intermediate and 8 (6%) as high risk. FLIPI identified 99 patients (70%) at low risk, 35 (24%) at intermediate and 9 (6%) at high risk. After a median follow-up time of 39.5 months, 123 patients were alive and 46 patients had relapsed (median time to relapse 27 months). IPI significantly correlated with time to relapse, with the typical differentiation into low, low-intermediate and high risk groups. FLIPI divided patients into three groups, but the low and intermediate risk groups showed a similar clinical course. In terms of additional progonostic factors, univariate analysis suggested autoimmune disease and multifocal disease as correlated with relapse. Multiple regression analysis, however, identified only extragastric disease as predictive of relapse (p=0.001). CONCLUSION: Our data demonstrate that both IPI and FLIPI are able to discriminate prognostic subgroups in patients with MALT-lymphoma. However, the low and intermediate group of the FLIPI did not appear to prognostically differ.
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Linfoma de Células B de la Zona Marginal/clasificación , Linfoma de Células B de la Zona Marginal/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Anciano , Femenino , Indicadores de Salud , Humanos , Agencias Internacionales , Linfoma de Células B de la Zona Marginal/mortalidad , Linfoma Folicular , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Hematopoietic stem cells (HSCs) are generally defined by their dual properties of pluripotency and extensive self-renewal capacity. However, a lack of experimental clarity as to what constitutes extensive self-renewal capacity coupled with an absence of methods to prospectively isolate long-term repopulating cells with defined self-renewal activities has made it difficult to identify the essential components of the self-renewal machinery and investigate their regulation. We now show that cells capable of repopulating irradiated congenic hosts for 4 months and producing clones of cells that can be serially transplanted are selectively and highly enriched in the CD150(+) subset of the EPCR(+)CD48(-)CD45(+) fraction of mouse fetal liver and adult bone marrow cells. In contrast, cells that repopulate primary hosts for the same period but show more limited self-renewal activity are enriched in the CD150(-) subset. Comparative transcriptome analyses of these 2 subsets with each other and with HSCs whose self-renewal activity has been rapidly extinguished in vitro revealed 3 new genes (VWF, Rhob, Pld3) whose elevated expression is a consistent and selective feature of the long-term repopulating cells with durable self-renewal capacity. These findings establish the identity of a phenotypically and molecularly distinct class of pluripotent hematopoietic cells with lifelong self-renewal capacity.
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Separación Celular/métodos , Citometría de Flujo/métodos , Células Madre Hematopoyéticas/citología , Animales , Animales Congénicos , Antígenos CD/análisis , Antígenos de Diferenciación/análisis , Células de la Médula Ósea/citología , División Celular , Células Cultivadas/trasplante , Perfilación de la Expresión Génica , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/metabolismo , Inmunofenotipificación , Antígenos Comunes de Leucocito/análisis , Hígado/citología , Hígado/embriología , Ratones , Ratones Endogámicos C57BL , Fosfolipasa D/análisis , Quimera por Radiación , Receptores de Superficie Celular/análisis , Miembro 1 de la Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Proteína de Unión al GTP rhoB/análisis , Proteína de Unión al GTP rhoB/genética , Factor de von Willebrand/análisis , Factor de von Willebrand/genéticaRESUMEN
Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises approximately 7% of all newly diagnosed non-Hodgkin's lymphoma. It is mainly located in the stomach and has become a focus of interest due to its unique pathophysiological link with Helicobacter pylori (HP) and the consecutive response to HP eradication therapy. In view of this, HP eradication has become standard treatment for patients with localised disease, and recent data have suggested that HP-negative patients might benefit from antibiotic treatment. In case of non-response, however, the standard approach in such patients is unclear. Both radiation and chemotherapy have shown promising results, and at present there is only one randomised study, which nevertheless suggests chemotherapy as management of choice. The objective of this review is, therefore, to summarise and evaluate the data available for treatment of gastric MALT lymphoma and to highlight potential focus for further research.
Asunto(s)
Linfoma de Células B de la Zona Marginal/terapia , Neoplasias Gástricas/terapia , Terapia Combinada , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/radioterapia , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/radioterapiaRESUMEN
PURPOSE: Subclinical dissemination as well as persistence after therapy may be difficult to assess on clinical and histologic examinations in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. We have analyzed the use of reverse transcription-PCR (RT-PCR) for the detection of t(11;18)(q21;q21) in histologically infiltrated and normal biopsies at diagnosis and during follow-up to determine its clinical and prognostic effect. EXPERIMENTAL DESIGN: Twenty-one patients with t(11;18)(q21;q21)+ MALT lymphoma were included in this retrospective study. Presence of t(11;18)(q21;q21) was determined by RT-PCR done on 316 biopsies of various tissues obtained during staging and follow-up. RESULTS: Infiltration with lymphoma was histologically detected in 67 of 316 biopsies, whereas molecular infiltration was established in 104 of 316 biopsies. All histologically positive specimens were also positive in RT-PCR. There was a good concordance (P = 0.0001) between histology and RT-PCR at the time of disease presentation with only one further infiltration site identified by RT-PCR. In 8 of 12 patients with persistent lymphoma, RT-PCR revealed tumor infiltration in histologically unsuspected sites. Eight of nine treated patients with histologic and clinical complete remission (CR) remained RT-PCR positive. CR on RT-PCR was achieved later than histologic CR (between 13-59 months) without any further therapy in five of these eight patients; only one patient with persistent t(11;18)(q21;q21) relapsed histologically. CONCLUSIONS: This study shows the potential of RT-PCR for t(11;18)(q21;q21) done on routine paraffin-embedded specimens to identify disseminated disease in tissues otherwise not diagnostic of MALT lymphoma involvement. T(11;18)(q21;q21) persistence in patients with clinical and histologic CR does not necessarily require therapeutic intervention.