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1.
Oncogene ; 36(29): 4224-4232, 2017 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-28368397

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.


Asunto(s)
Linfoma de Células B Grandes Difuso/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Subunidad p52 de NF-kappa B/metabolismo , Linfocitos B/inmunología , Humanos , Activación de Linfocitos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Subunidad p50 de NF-kappa B/genética , Subunidad p50 de NF-kappa B/inmunología , Subunidad p52 de NF-kappa B/genética , Subunidad p52 de NF-kappa B/inmunología , Fenotipo , Transducción de Señal
2.
Br J Cancer ; 112(6): 963-70, 2015 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-25742472

RESUMEN

BACKGROUND: Mutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (±mitomycin C) in the randomised phase III MAX study. METHODS: DNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM. RESULTS: Of the available 280 of the 471 (59.4%) patients, mutations in KRAS exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The PIK3CA MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.71-1.17)) or OS (HR 0.95 (0.71-1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37-0.85) for RAS MT and HR 0.69 (0.5-0.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic. CONCLUSION: Of KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Genes ras , Mutación , Fosfatidilinositol 3-Quinasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Capecitabina , Fosfatidilinositol 3-Quinasa Clase I , Neoplasias Colorrectales/patología , ADN de Neoplasias/química , ADN de Neoplasias/genética , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Masculino , Mitomicina/administración & dosificación , Pronóstico
3.
Intern Med J ; 44(5): 458-63, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24612257

RESUMEN

BACKGROUND: Anticancer drugs are often expensive and are contributing to the growing cost of cancer care. Concerns have been raised about the effect rising costs may have on availability of new anticancer drugs. AIM: This study aims to determine the recent changes in the costs of anticancer drugs in Australia. METHODS: Publicly available expenditure and prices paid by the Australian Pharmaceutical Benefits Scheme (PBS) for anticancer drugs from 2000 to 2012 were reviewed. The measures used to determine changes in cost were total PBS expenditure and average price paid by the PBS per prescription for anticancer drugs and for all PBS listed drugs. An estimated monthly price paid for newly listed anticancer drugs was also calculated. RESULTS: Annual PBS expenditure on anticancer drugs rose from A$65 million in 1999-2000 to A$466 million in 2011-2012; an average increase of 19% per annum. The average price paid by the PBS per anticancer drug prescription, adjusted for inflation, increased 133% from A$337 to A$786. The real average annual increase in the price per anticancer drug prescription was more than double that for all other PBS drugs combined (7.6% vs 2.8%, difference 4.8%, 95% confidence interval -0.4% to 10.1%, P = 0.07). The median price for a month's treatment of the new anticancer drugs listed was A$4919 (range A$1003 to A$12 578, 2012 prices). CONCLUSIONS: PBS expenditure and the price of anticancer drugs in Australia rose substantially from 2000 to 2012. Dealing with these burgeoning costs will be a major challenge for our health system and for those affected by cancer.


Asunto(s)
Antineoplásicos/economía , Costos de los Medicamentos/tendencias , Seguro de Servicios Farmacéuticos/economía , Antineoplásicos/provisión & distribución , Australia , Utilización de Medicamentos , Humanos , Inflación Económica , Neoplasias/tratamiento farmacológico , Neoplasias/economía
4.
Int Urogynecol J ; 25(4): 451-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24504066

RESUMEN

INTRODUCTION AND HYPOTHESIS: This study was undertaken to investigate the relationship between symptoms of prolapse and International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) measurements in order to establish optimal cutoffs for predicting prolapse symptoms using receiver operator characteristic (ROC) statistics. METHODS: This was a retrospective study using 764 archived data sets of patients seen for symptoms of lower urinary tract and pelvic floor dysfunction between March 2011 and November 2012. Main outcome measure was symptoms of prolapse. Explanatory parameters were Ba, C, and Bp as defined by the ICS POP-Q. Patient age, body mass index (BMI), previous hysterectomy or incontinence/prolapse surgery, and vaginal parity were tested for a confounding effect on the relationship between ICS POP-Q measurements and symptoms of prolapse. RESULTS: Optimal cutoffs for predicting prolapse symptoms were defined as follows: Ba = -0.5 (sensitivity 69 %, specificity 71 %), C =-5 (sensitivity 67 %, specificity 64 %), Bp = -0.5 (sensitivity 63 %, specificity 62 %). ROC statistics resulted in an area under the curve of 0.768 for Ba [confidence interval (CI) 0.729-0.807), for C of 0.724 (CI 0.672-0.776), and for Bp of 0.686 (CI 0.639-0.733). CONCLUSION: Our findings suggest that the ICS POP-Q staging system requires revision. Prolapse of the anterior and posterior vaginal wall of < -1 should probably be regarded as normal. On the other hand, stage 1 uterine prolapse as currently defined seems highly relevant.


Asunto(s)
Prolapso de Órgano Pélvico/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
5.
Bone Marrow Transplant ; 42(8): 529-34, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18622414

RESUMEN

Autologous hematopoietic progenitor SCT (HPCT) has been studied both as a consolidative and salvage maneuver in mantle-cell lymphoma (MCL), and may improve failure-free survival rates as well as overall survival. We describe 21 patients with MCL who received autologous HPCT at Emory University Hospital as part of the primary treatment strategy. Sixteen patients were in CR1 and five in PR1 at the time of HPCT. The most commonly used induction chemotherapy was the hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimen with or without rituximab. At the last follow-up, 17 patients were in continuous CR, and there were four relapses. There were no transplant-related deaths. With a median follow-up of 54 months from HPCT, 5-year progression-free survival and overall survival are 73% and 76%, respectively. Our retrospective analysis provides the longest follow-up to date for patients with MCL who received an autologous HPCT as part of primary treatment. This lengthy follow-up helps define the natural course of MCL after autologous transplantation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Terapia Recuperativa , Tasa de Supervivencia , Trasplante Autólogo , Vincristina/administración & dosificación
6.
Diagn Cytopathol ; 24(1): 1-10, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11135461

RESUMEN

Although fine-needle aspiration (FNA) is accepted as the method of choice for the initial evaluation of lymph nodes for metastatic carcinomas, its utility as the initial diagnostic procedure for hematopoietic processes is less established. We review our experience over a 3-year period with 127 FNA cases accompanied by flow cytometric (FC) analysis from 117 patients. Fifty cases had subsequent histologic examination. A hematopoietic process was identified in 85 cases, a reactive process in 27 cases, and a nonhematopoietic process in 15 cases. All non-Hodgkin lymphomas (NHL) were B-cell processes except for one T-cell lymphoma. By FNA/FC, 44 NHL had sufficient findings to be subtyped; of these, 27 had subsequent histologic examination. The correlation between the FNA/FC and histologic classification in these cases of NHL was 100%. One case was insufficient for diagnosis by FNA and six cases were inadequate for FC. We conclude that FNA in conjunction with FC can be used as the initial diagnostic approach for both primary and recurrent hematopoietic processes.


Asunto(s)
Linfoma no Hodgkin/diagnóstico , Biopsia con Aguja , Citometría de Flujo , Humanos , Inmunofenotipificación , Ganglios Linfáticos/patología , Metástasis Linfática , Linfoma no Hodgkin/clasificación , Reproducibilidad de los Resultados
7.
Cancer Genet Cytogenet ; 116(1): 74-6, 2000 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-10616537

RESUMEN

We report a case of AML-M5 with tetrasomy 8 that evolved within a 7-month period to a segmental triplication 8q. Other numerical abnormalities in the initial diagnosis were not found at the relapse; however, a chromosome 1 structural abnormality was maintained, proving the clonal evolution from tetrasomy 8 to a segmental triplication of the long arm of 8. This strongly suggests that there is a functional and selective advantage for duplications and triplications of 8q in these patients.


Asunto(s)
Aneuploidia , Cromosomas Humanos Par 8 , Leucemia Monocítica Aguda/genética , Anciano , Biopsia , Médula Ósea/patología , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 5 , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino
8.
J Clin Oncol ; 17(1): 293-7, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10458245

RESUMEN

PURPOSE: Blast expression of CD56 is frequent in patients with t(8;21)(q22;q22) acute myeloid leukemia and is associated with an inferior outcome. The expression of CD56 has rarely been reported in acute promyelocytic leukemia (APL) and has not been clinically characterized. Therefore, we examined the prognostic significance of CD56 expression in APL. PATIENTS AND METHODS: We identified all reported cases of CD56+ APL in the medical literature and collected clinical, biologic, and therapeutic details. RESULTS: Data were obtained for 12 patients with CD56+ APL (> 20% blast expression of CD56), including four cases from a single institution with a total of 42 APL patients. All of the CD56+ APL patients had documented cytogenetic presence of t(15;17), and of the nine reported isotypes, eight (89%) were S-isoform. Only six CD56+ patients (50%) attained complete remission (CR); the other six individuals died within 35 days of presentation. Of the six patients who attained a CR, three (50%) relapsed at 111, 121, and 155 weeks, whereas three remained in continuous CR at 19, 90, and 109 weeks. Comparison of the control CD56- to CD56+ APL patients demonstrated that the latter group had a significantly lower fibrinogen level (P = .007), and among patients for whom data were available, there was a higher frequency of the S-isoform (P = .006). Additionally, the CR rate (50% v 84%, P = .025) and overall median survival (5 v 232 weeks; P = .019) were significantly inferior for CD56+ APL patients. CONCLUSION: CD56+ acute promyelocytic leukemia is infrequent, seems to occur more frequently with the S-isoform subtype, and may be associated with a lower CR rate and inferior overall survival.


Asunto(s)
Antígeno CD56/análisis , Leucemia Promielocítica Aguda/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunofenotipificación , Leucemia Promielocítica Aguda/inmunología , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
9.
Diagn Cytopathol ; 21(2): 98-104, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10425046

RESUMEN

Cytomorphology in conjunction with immunophenotypic characterization is becoming increasingly used for the primary diagnosis of non-Hodgkin's lymphomas (NHL). This combination is especially advantageous for the diagnosis of intra-abdominal and intrathoracic lymphomas, since unlike superficial lesions, open biopsy of deep-seated tissues is more invasive and more costly, and is associated with a higher risk. We report the cytologic and immunophenotypic features of intra-abdominal NHL obtained by fine-needle aspiration (FNA). Twenty-two cases of intra-abdominal lesions obtained by image-guided FNA where flow cytometry was also performed were reviewed. Of the 22 studied cases, 7 were classified as large-cell lymphoma, 5 as follicular center-cell lymphoma, 2 as small noncleaved-cell lymphoma, 2 as lymphoplasmacytoid lymphoma, one as small lymphocytic lymphoma, and one as marginal-zone lymphoma. In the remaining 4 cases where the immunophenotypic pattern was not definitive, the cytomorphologic features were of small cleaved cells in 3 cases and of mixed small cleaved and large cells in one case. We successfully classified 9 of the 10 patients on whom histologic confirmation was obtained. The successful primary classification of most intra-abdominal non-Hodgkin's lymphomas can be done with a combination of cytology and flow cytometry, and this can be the initial approach in patients with deep-seated lesions. Diagn. Cytopathol. 1999;21:98-104.


Asunto(s)
Neoplasias Abdominales/diagnóstico , Biopsia con Aguja , Inmunofenotipificación/métodos , Linfoma no Hodgkin/diagnóstico , Neoplasias Retroperitoneales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad
10.
Leuk Lymphoma ; 33(3-4): 377-84, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10221519

RESUMEN

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.


Asunto(s)
Antígenos CD/análisis , Linfocitos T CD8-positivos/inmunología , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 6 , Trasplante de Riñón , Linfoma de Células T/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/biosíntesis , Antígenos CD/genética , Antineoplásicos/uso terapéutico , Médula Ósea/inmunología , Médula Ósea/patología , Médula Ósea/virología , Antígenos CD8/análisis , Cladribina/uso terapéutico , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/cirugía , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/etiología , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Receptores de Antígenos de Linfocitos T gamma-delta/genética
11.
Diagn Cytopathol ; 20(2): 85-9, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9951604

RESUMEN

We describe a patient who developed granulocytic sarcomas of the mesentery and breast approximately 4 yrs following an allogenic bone marrow transplantation for acute myeloblastic leukemia. The diagnosis was made by a combination of fine-needle aspiration cytology and flow cytometry. The differential diagnoses of localized masses in posttransplant patients and how the combination of fine-needle aspiration cytology and flow cytometry may be used are discussed.


Asunto(s)
Trasplante de Médula Ósea , Neoplasias de la Mama/patología , Leucemia Mieloide/patología , Mesenterio , Neoplasias Peritoneales/patología , Adulto , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biopsia con Aguja , Examen de la Médula Ósea , Neoplasias de la Mama/metabolismo , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Leucemia Mieloide/metabolismo , Neoplasias Peritoneales/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Lectina 3 Similar a Ig de Unión al Ácido Siálico
12.
Ear Nose Throat J ; 77(10): 855-8, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9818538

RESUMEN

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare histiocytosis of unknown etiology that most commonly involves the cervical lymph nodes. Extranodal involvement occurs in 30-40% of cases, most often in the head and neck. Characteristic histologic findings include emperiopolesis (engulfment) of lymphocytes and S-100 protein positivity. Treatment of Rosai-Dorfman disease is unnecessary unless the disorder becomes life- or organ-threatening, since the disease will resolve spontaneously in most patients. We present what, to the best of our knowledge, is the first reported case of Rosai-Dorfman disease limited to the skin in a patient infected with human immunodeficiency virus. SHML is described and diagnostic and therapeutic measures are reviewed.


Asunto(s)
Seropositividad para VIH/complicaciones , Histiocitosis Sinusal/complicaciones , Histiocitosis Sinusal/diagnóstico , Adulto , Histiocitosis Sinusal/cirugía , Humanos , Masculino , Cavidad Nasal/patología , Cavidad Nasal/cirugía
13.
Ann Med ; 30(4): 323-44, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9783831

RESUMEN

In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Linfoma Relacionado con SIDA , Sarcoma de Kaposi , Neoplasias Urogenitales , Femenino , Humanos , Masculino
14.
Diagn Cytopathol ; 19(3): 205-9, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9740997

RESUMEN

We describe a patient with agnogenic myeloid metaplasia and Sjogren's disease who developed a large B-cell lymphoma. We discuss the differential diagnoses of fine-needle aspirations of a localized mass from such patients and review the literature of the association between agnogenic myeloid metaplasia and lymphoma.


Asunto(s)
Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Mielofibrosis Primaria/complicaciones , Anciano , Biopsia con Aguja , Diagnóstico Diferencial , Femenino , Humanos , Ganglios Linfáticos/patología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Mielofibrosis Primaria/patología , Síndrome de Sjögren/complicaciones , Esplenomegalia/etiología , Esplenomegalia/patología
15.
Am J Clin Pathol ; 107(6): 653-60, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9169661

RESUMEN

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.


Asunto(s)
Antígeno CD56/metabolismo , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/patología , Proto-Oncogenes , Factores de Transcripción , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Proteínas de Unión al ADN/genética , Femenino , Citometría de Flujo , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Proteína de la Leucemia Mieloide-Linfoide , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/metabolismo , Análisis de Supervivencia , Resultado del Tratamiento
16.
J Pediatr Hematol Oncol ; 19(1): 73-6, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9065723

RESUMEN

PURPOSE: Sodium valproate is commonly used as an anticonvulsant for patients with refractory epilepsy. Hematopoietic toxicity involving platelets or erythrocytes has been previously described, as well as a few cases of generalized bone marrow suppression. PATIENTS AND METHODS: We report an infant receiving sodium valproate who developed severe anemia and thrombocytopenia, numerous circulating immature myeloid cells, and a coagulopathy. Bone marrow aspirate revealed approximately 40% abnormal promyelocytes, and the initial clinical and pathologic interpretation was consistent with the diagnosis of acute promyelocytic leukemia. RESULTS: Antineoplastic therapy was withheld while valproate was weaned. All hematopoietic abnormalities resolved after valproate therapy was discontinued. CONCLUSION: This report expands the clinical spectrum of hematopoietic toxicity associated with sodium valproate. Drug toxicity should be considered in any patient on valproate who develops hematopoietic abnormalities.


Asunto(s)
Linaje de la Célula/efectos de los fármacos , GABAérgicos/efectos adversos , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Leucemia Promielocítica Aguda/tratamiento farmacológico , Ácido Valproico/efectos adversos , Niño , Femenino , GABAérgicos/uso terapéutico , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Ácido Valproico/uso terapéutico
17.
Cytometry ; 26(2): 172-7, 1996 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-8817095

RESUMEN

Development of a more cost-effective and efficient method of performing lymphocyte subset analysis is of continuing importance in clinical flow cytometry laboratories. Current two-color methods utilize forward and right angle light scatter and multiple tubes per sample and are thereby liable to gate contamination. Methods using three-color analysis with CD45 vs. right angle light scatter (RALS) gating cannot always exclude a contaminating nonlymphoid population. We have established a two tube approach to directly measure total T cells, T suppressor, and T helper subsets, total B cells and total natural killer cells. The technique involves staining of whole blood with a mixture of five monoclonal antibodies conjugated to three fluorochromes: CD4+CD19 fluorescein isothiocyanate (FITC), CD3+CD33 phycoerythrin (PE), CD45 peridin chlorophyll alpha protein (PerCP), CD8+CD16 FITC, CD3+CD33 PE, and CD45 PerCP. Analysis is performed using a single laser flow cytometer. This method has equivalent recovery to and improved purity of the lymphocyte gate when compared to well-established methods. These antibody combinations additionally allow clear separation of lymphocytes from other leukocytes and debris as well as separation of the T cell helper and suppressor subsets, natural killer cells and B lymphocytes. We additionally provide preliminary data that an accurate lymphocyte subset analysis can be performed on a single tube containing five antibodies (CD4+CD19 FITC, CD3+CD33 PE, and CD45 PerCP), although some measurements are performed deductively.


Asunto(s)
Antígenos CD/análisis , Citometría de Flujo/métodos , Subgrupos Linfocitarios/clasificación , Subgrupos Linfocitarios/inmunología , Humanos
18.
Am J Surg Pathol ; 19(4): 407-16, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7694942

RESUMEN

The presence of neutrophils, in the absence of necrosis, is uncommon in malignant lymphoma (ML). We identified a subgroup of Ki-1-positive anaplastic large cell ML (Ki-1 ALCL) in which neutrophils were a prominent component. Six of 20 cases of Ki-1 ALCL had a significant neutrophil infiltrate that varied from 5 to 10% to > 50% of cells per high power field. Neutrophils were not seen in 100 cases of other types of ML reviewed. Patients were first seen with skin lesions (four), localized lymphadenopathy (three), generalized lymphadenopathy (one), and localized extranodal disease (one). All had primary disease. Two patients had peripheral neutrophilia. Three of six patients had clinical stage IV disease. Four patients are currently in clinical remission; one died of recurrent disease; and one patient with acquired immunodeficiency syndrome (AIDS) died of Pneumocystis carinii pneumonia. Four cases demonstrated a T-cell phenotype, one of which arose in a patient with AIDS. Two had a B-cell phenotype. All cases were positive for CD30 (Ki-1). These observations expand the morphologic spectrum of Ki-1 ALCL to include a neutrophil-rich variant. We conclude that the presence of neutrophils is another morphologic feature shared by some cases of Ki-1 ALCL, lymphomatoid papulosis, and Hodgkin's disease, which suggests a possible pathogenetic link among them.


Asunto(s)
Linfoma Anaplásico de Células Grandes/patología , Neutrófilos/patología , Adulto , Anciano , Femenino , Genotipo , Humanos , Inmunofenotipificación , Linfoma Anaplásico de Células Grandes/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología
19.
Mol Cell Biol ; 13(4): 2411-9, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8384308

RESUMEN

The recognition and processing of a pre-mRNA to create a poly(A) addition site, a necessary step in mRNA biogenesis, can also be a regulatory event in instances in which the frequency of use of a poly(A) site varies. One such case is found during the course of an adenovirus infection. Five poly(A) sites are utilized within the major late transcription unit to produce more than 20 distinct mRNAs during the late phase of infection. The proximal half of the major late transcription unit is also expressed during the early phase of a viral infection. During this early phase of expression, the L1 poly(A) site is used three times more frequently than the L3 poly(A) site. In contrast, the L3 site is used three times more frequently than the L1 site during the late phase of infection. Recent experiments have suggested that the recognition of the poly(A) site GU-rich downstream element by the CF1 processing factor may be a rate-determining step in poly(A) site selection. We demonstrate that the interaction of CF1 with the L1 poly(A) site is less stable than the interaction of CF1 with the L3 poly(A) site. We also find that there is a substantial decrease in the level of CF1 activity when an adenovirus infection proceeds to the late phase. We suggest that this reduction in CF1 activity, coupled with the relative instability of the interaction with the L1 poly(A) site, contributes to the reduced use of the L1 poly(A) site during the late stage of an adenovirus infection.


Asunto(s)
Infecciones por Adenoviridae/genética , Adenovirus Humanos/genética , Regulación Viral de la Expresión Génica , Poli A/metabolismo , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , ARN Viral/genética , Proteínas de Unión al ARN/metabolismo , Secuencia de Bases , Células HeLa , Humanos , Datos de Secuencia Molecular , Factores de Escisión y Poliadenilación de ARNm
20.
J Virol ; 61(7): 2100-8, 1987 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3035211

RESUMEN

In this paper we describe the posttranslational processing of the p63/LMP (latent membrane protein) encoded by Epstein-Barr virus in transformed B cells. Specifically, we show that after synthesis, free LMP disappeared with a half-life of about 0.5 h. This was caused by the association of LMP with an insoluble complex. All detectable LMP in the plasma membrane was insoluble. This interaction was resistant to nondenaturing detergents but readily dissociated with 8 M urea or by boiling in 0.5% sodium dodecyl sulfate, suggesting that LMP may be associated with cytoskeletal elements. Most of the Nonidet P-40-insoluble LMP was phosphorylated (ppLMP) primarily on serine but also on threonine residues. No phosphotyrosine was detected. Furthermore, greater than 90% of the ppLMP resided in the Nonidet P-40-insoluble fraction, suggesting a strong correlation between complexing and phosphorylation. Additionally, ppLMP was found to be associated with a 53,000-molecular-weight phosphoprotein (pp53) of unknown origin. Finally, LMP turned over extremely rapidly, with a half-life of about 2 h. Taken together, these properties suggest that although LMP falls broadly within the category of phosphorylated, cytoskeleton-associated oncoproteins, it is nevertheless clearly different from any previously described member of this family.


Asunto(s)
Herpesvirus Humano 4/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas Virales/biosíntesis , Aminoácidos/análisis , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Línea Celular , Membrana Celular/análisis , Citoesqueleto/análisis , Detergentes , Semivida , Herpesvirus Humano 4/inmunología , Humanos , Focalización Isoeléctrica , Linfocitos/análisis , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/aislamiento & purificación , Procesamiento Proteico-Postraduccional , Solubilidad , Proteínas Virales/inmunología , Proteínas Virales/aislamiento & purificación
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