RESUMEN
Therapeutic management and prognostication for patients with B-acute lymphoblastic leukaemia (B-ALL) require appropriate disease subclassification. BCR::ABL1-like B-ALL is unique in that it is defined by a gene expression profile similar to BCR::ABL1+ B-ALL rather than a unifying recurrent translocation. Current molecular/cytogenetic techniques to identify this subtype are expensive, not widely accessible, have long turnaround times and/or require an adequate liquid biopsy. We have studied a total of 118 B-ALL cases from three institutions in two laboratories to identify surrogates for BCR::ABL1+/like B-ALL. We report that immunoglobulin joining chain (IGJ) and spermatogenesis associated serine-rich 2-like (SPATS2L) immunohistochemistry (IHC) sensitively and specifically identify BCR::ABL1+/like B-ALL. IGJ IHC positivity has a sensitivity of 83%, a specificity of 95%, a positive predictive value (PPV) of 89% and a negative predictive value (NPV) of 90%. SPATS2L staining has similar sensitivity and NPV but lower specificity (85%) and PPV (70%). The presence of either IGJ or SPATS2L staining augments the sensitivity (93%) and NPV (95%). While these findings would need to be validated in larger studies, they suggest that IGJ and/or SPATS2L IHC may be utilized in identifying BCR::ABL1-like B-ALL or in selecting B-ALL cases for confirmatory molecular/genetic testing, particularly in resource-limited settings.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Inmunohistoquímica , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Translocación GenéticaRESUMEN
The ability to detect low-level disease is key to our understanding of clonal heterogeneity in acute myeloid leukemia (AML) and residual disease that elude conventional assays and seed relapse. We developed a high-sensitivity next-generation sequencing (HS-NGS) clinical assay, able to reliably detect low levels (1 × 10-5) of FLT3-ITD, a frequent, therapeutically targetable and prognostically relevant mutation in AML. By applying this assay to 289 longitudinal samples from 62 patients at initial diagnosis and/or clinical follow-up (mean follow-up of 22 months), we reveal the frequent occurrence of FLT3-ITD subclones at diagnosis and demonstrate a significantly decreased relapse risk when FLT3-ITD is cleared after induction or thereafter. We perform pairwise sequencing of diagnosis and relapse samples from 23 patients to uncover more detailed patterns of FLT3-ITD clonal evolution at relapse than is detectable by less-sensitive assays. Finally, we show that rising ITD level during consecutive biopsies is a harbinger of impending relapse. Our findings corroborate the emerging clinical utility of high-sensitivity FLT3-ITD testing and expands our understanding of clonal dynamics in FLT3-ITD-positive AML.
RESUMEN
Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially erythrocytes and platelets. The latter is important since this protein may work as negative regulator of granule release. Thus, we sought to begin to understand the structure of this protein in platelets. Flow cytometric analysis of this protein using region-specific (N-terminus, central region and C-terminus) monoclonal antibodies was performed. Antibody to the central region gave the strongest shift among all three antibodies, with the C-terminus having intermediate shift and N-terminus minimal shift. Western blotting using the same antibodies showed similar binding of all antibodies to α-synuclein. These results suggest a similar arrangement of this protein in platelets as seen in neurons. Future studies ought to look at the role that each protein region plays in platelets.
Asunto(s)
Plaquetas , alfa-Sinucleína , Anticuerpos Monoclonales , Plaquetas/metabolismo , Citometría de Flujo , Humanos , alfa-Sinucleína/análisis , alfa-Sinucleína/metabolismoRESUMEN
Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
Asunto(s)
Linfoma de Burkitt/genética , Secuenciación Completa del Genoma/métodos , Animales , Humanos , RatonesRESUMEN
OBJECTIVES: Although morphologic dysplasia is not typically considered a feature of CCUS, we have consistently observed low-level bone marrow (BM) dysplasia among CCUS patients. We sought to determine whether sub-diagnostic BM dysplasia in CCUS patients is associated with other clinico-pathologic findings of myelodysplastic syndrome (MDS). METHODS: We identified 49 CCUS patients, 25 with sub-diagnostic dysplasia (CCUS-D), and 24 having no dysplasia (CCUS-ND). We compared the clinical, histologic, and laboratory findings of CCUS-D and CCUS-ND patients to 49 MDS patients, including blood cell counts, BM morphology, flow cytometry, cytogenetics, and results of next-generation sequencing. RESULTS: No statistically significant differences were observed between CCUS-D and CCUS-ND patients in the degree of cytopenias, BM cellularity, myeloid-to-erythroid ratio, or the presence of flow cytometric abnormalities. However, compared to CCUS-ND, CCUS-D patients exhibited increased mutations in myeloid malignancy-associated genes, including non-TET2/DNMT3A/ASXL1 variants, spliceosome (SF3B1, SRSF2, ZRSR2, or U2AF1) variants, and IDH2/RUNX1/CBL variants. CCUS-D patients were also enriched for higher variant allele frequencies and co-mutation of TET2/DNMT3A/ASXL1 with other genes. CONCLUSIONS: CCUS-D patients exhibit a molecular (but not clinical) profile more similar to MDS patients than CCUS-ND, suggesting CCUS-D may represent a more immediate precursor to MDS and may warrant closer clinical follow-up.
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Síndromes Mielodisplásicos/diagnóstico , Pancitopenia/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores , Biopsia , Médula Ósea , Evolución Clonal , Hematopoyesis Clonal , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Citometría de Flujo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/etiología , Pancitopenia/sangre , Pancitopenia/etiología , FenotipoAsunto(s)
Eosinofilia , Leucemia Mieloide Aguda , Mutación , Factor de Transcripción STAT5 , Humanos , Factor de Transcripción STAT5/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Eosinofilia/genética , Eosinofilia/patología , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Femenino , Transformación Celular Neoplásica/genéticaRESUMEN
Fanconi anemia (FA) is an autosomal recessive, progressive bone marrow failure disorder characterized by congenital defects and marked cancer predisposition. Hematopoietic stem cell transplant is the therapy of choice for FA patients with progressive pancytopenia. These patients receive multiple transfusions for cytopenias. Oxymetholone has been used with variable success to improve cytopenias. Eltrombopag has been shown to induce bilineage or trilineage hematopoiesis in aplastic anemia and patients with myelodysplastic marrow. We report a case of FA where eltrombopag in conjunction with oxymetholone induced trilineage hematopoiesis and eliminated transfusion requirement before transplant, thereby enhancing favorable outcome after hematopoietic stem cell transplant.
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Benzoatos/farmacología , Anemia de Fanconi/terapia , Hematopoyesis/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas , Hidrazinas/farmacología , Pirazoles/farmacología , Quimioterapia Combinada , Anemia de Fanconi/complicaciones , Humanos , Oximetolona/uso terapéutico , Pancitopenia/etiologíaRESUMEN
Gain-of-function (GOF) mutations of protein tyrosine phosphatase nonreceptor type 11 Ptpn11 (Shp2), a protein tyrosine phosphatase implicated in multiple cell signaling pathways, are associated with childhood leukemias and solid tumors. The underlying mechanisms are not fully understood. Here, we report that Ptpn11 GOF mutations disturb mitosis and cytokinesis, causing chromosomal instability and greatly increased susceptibility to DNA damage-induced malignancies. We find that Shp2 is distributed to the kinetochore, centrosome, spindle midzone, and midbody, all of which are known to play critical roles in chromosome segregation and cytokinesis. Mouse embryonic fibroblasts with Ptpn11 GOF mutations show a compromised mitotic checkpoint. Centrosome amplification and aberrant mitosis with misaligned or lagging chromosomes are significantly increased in Ptpn11-mutated mouse and patient cells. Abnormal cytokinesis is also markedly increased in these cells. Further mechanistic analyses reveal that GOF mutant Shp2 hyperactivates the Polo-like kinase 1 (Plk1) kinase by enhancing c-Src kinase-mediated tyrosine phosphorylation of Plk1. This study provides novel insights into the tumorigenesis associated with Ptpn11 GOF mutations and cautions that DNA-damaging treatments in Noonan syndrome patients with germ-line Ptpn11 GOF mutations could increase the risk of therapy-induced malignancies.
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Daño del ADN , Mitosis , Neoplasias/etiología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/fisiología , Animales , Proteínas de Ciclo Celular/metabolismo , Inestabilidad Cromosómica , Humanos , Ratones , Ratones Endogámicos C57BL , Mutación , Neoplasias/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteínas Proto-Oncogénicas/metabolismo , Quinasa Tipo Polo 1RESUMEN
We report an individual with a compound heterozygosity for Hb D-Ibadan (HBB: c.263C>A) and Hb C (HBB: c.19G>A), a hemoglobin (Hb) combination not previously identified. The compound hemoglobinopathy was detected in a young woman during routine prenatal screening. Variant Hbs were identified and confirmed by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) followed by Sanger DNA sequencing. Hb D-Ibadan was present in significant excess over Hb C (70.3 to 24.4%). A complete blood count (CBC) revealed moderate microcytosis with slight anemia. The history suggests the Hb combination is clinically silent. The findings indicate the compound hemoglobinopathy demonstrates thalassemia minor-like red cell indices with an unequal distribution of the variant Hbs. Comparison with other Hb D-like heterozygous conditions is reviewed.
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Hemoglobina C/genética , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Heterocigoto , Recuento de Células Sanguíneas , Femenino , Humanos , Embarazo , Diagnóstico Prenatal , Análisis de Secuencia de ADNRESUMEN
Extranodal marginal zone lymphoma (EMZL) is a B-cell lymphoma arising from mucosa-associated lymphoid tissue (MALT). The disease characteristics, clinical course and treatment vary considerably based on site of involvement. Because long-term outcome data for EMZL are limited, we sought to describe the clinical details of a large number of patients with EMZL evaluated at the Case Comprehensive Cancer Center over a 12-year period to identify prognostic markers including the impact of site of involvement. We identified 211 cases of EMZL involving the stomach (30%), ocular adnexa (19%), lungs (16%) and intestines (9%). Initial treatment included antibiotics (18%), radiation (21%), rituximab (20%), chemotherapy (3%), rituximab + chemotherapy (7%), surgery (17%) or observation (8%). After a median follow-up of 44·3 months (range 2·2-214·9), median progression-free survival (PFS) was 68·2 months (95% confidence interval [CI] 54·5-111·3) and median overall survival (OS) has not been reached. Age >60 years, elevated lactate dehydrogenase level (LDH), ≥4 lymph node groups involvement, and high follicular lymphoma international prognostic index (FLIPI) were associated with inferior PFS/OS. In summary, patients with EMZL have excellent prognosis with median OS in excess of 10 years. Age, elevated LDH, advanced disease, and high FLIPI score are associated with worse outcomes.
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Linfoma de Células B de la Zona Marginal/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , L-Lactato Deshidrogenasa/análisis , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin lymphoma that arises from mature B-cells. We delineate outcomes, prognostic factors and treatment trends among a large cohort of patients with NMZL in the rituximab era. We identified 56 such patients treated at our institutions. The majority presented with advanced stage disease (78·6%). Over a median follow-up of 38·2 months, median progression-free survival (PFS) was 42·4 months and median overall survival (OS) was not reached. Kaplan-Meier estimates of OS at 120 months after diagnosis was 71·9%. High-risk follicular lymphoma international prognostic index (FLIPI) was associated with inferior PFS. Age >60 years and elevated serum lactate dehydrogenase (LDH) were associated with inferior OS. Transformation to diffuse large B-cell lymphoma occurred in 7 patients, 6 of who presented with advanced disease. OS was comparable to our previously reported extranodal MZL cohort. FLIPI score predicted for inferior PFS and OS when both cohorts were analysed together (n = 267). In summary, outcomes in NMZL are favourable with a large majority of patients surviving at 120 months. High risk FLIPI, age >60 years, and elevated serum LDH were associated with inferior outcomes.
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Antineoplásicos/uso terapéutico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/mortalidad , Rituximab/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B de la Zona Marginal/diagnóstico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Rituximab/administración & dosificación , Resultado del Tratamiento , Adulto JovenAsunto(s)
Eosinofilia , Trastornos Mieloproliferativos , Neoplasias , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Eosinofilia/tratamiento farmacológico , Proteínas de Fusión bcr-abl , Humanos , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Proteínas de Fusión Oncogénica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/genéticaAsunto(s)
Antígeno Ki-1/análisis , Micosis Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Bexaroteno/administración & dosificación , Humanos , Antígeno Ki-1/metabolismo , Masculino , Persona de Mediana Edad , Micosis Fungoide/sangre , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/patología , Fotoféresis , Síndrome de Sézary/sangre , Síndrome de Sézary/tratamiento farmacológico , Síndrome de Sézary/patología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Linfocitos T/metabolismo , Resultado del Tratamiento , Vorinostat/administración & dosificaciónAsunto(s)
Anticuerpos Biespecíficos/administración & dosificación , Trasplante de Células Madre de Sangre del Cordón Umbilical , N-Metiltransferasa de Histona-Lisina , Proteína de la Leucemia Mieloide-Linfoide , Proteínas de Fusión Oncogénica , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Aloinjertos , Quimioterapia de Consolidación , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Lactante , Masculino , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapiaAsunto(s)
Biomarcadores de Tumor , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Biomarcadores , Humanos , Inmunohistoquímica , Inmunofenotipificación , Terapia Molecular Dirigida , Fenotipo , Linfoma Plasmablástico/tratamiento farmacológico , Linfoma Plasmablástico/metabolismo , Pronóstico , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismoRESUMEN
Microbial molecules or cytokines can stimulate dendritic cell (DC) maturation, which involves DC migration to lymph nodes and enhanced presentation of Ag to launch T cell responses. Microbial TLR agonists are the most studied inducers of DC maturation, but type I IFN (IFN-I) also promotes DC maturation. In response to TLR stimulation, DC maturation involves a burst of Ag processing with enhanced expression of peptide-class II MHC complexes and costimulator molecules. Subsequently, class II MHC (MHC-II) synthesis and expression in intracellular vacuolar compartments is inhibited, decreasing Ag processing function. This limits presentation to a cohort of Ags kinetically associated with the maturation stimulus and excludes presentation of Ags subsequently experienced by the DC. In contrast, our studies show that IFN-I enhances DC expression of MHC-II and costimulatory molecules without a concomitant inhibition of subsequent MHC-II synthesis and Ag processing. Expression of mRNA for MHC-II and the transcription factor CIITA is inhibited in DCs treated with TLR agonists but maintained in cells treated with IFN-I. After stimulation with IFN-I, MHC-II expression is increased on the plasma membrane but is also maintained in intracellular vacuolar compartments, consistent with sustained Ag processing function. These findings suggest that IFN-I drives a distinctive DC maturation program that enhances Ag presentation to T cells without a shutdown of Ag processing, allowing continued sampling of Ags for presentation.
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Presentación de Antígeno/inmunología , Células Dendríticas/citología , Antígenos de Histocompatibilidad Clase II/biosíntesis , Interferón Tipo I/fisiología , Adyuvantes Inmunológicos/farmacología , Animales , Diferenciación Celular , Células Dendríticas/efectos de los fármacos , Endocitosis , Regulación de la Expresión Génica/inmunología , Genes MHC Clase II , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Interferón Tipo I/farmacología , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos C57BL , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Fenotipo , Proteínas Recombinantes/farmacología , Inhibidores de la Transcriptasa Inversa , Organismos Libres de Patógenos Específicos , Receptores Toll-Like/agonistas , Transactivadores/biosíntesis , Transactivadores/genéticaRESUMEN
Lymphoplasmacytic lymphoma often needs to be differentiated from other B-cell lymphomas with plasmacytic differentiation, especially marginal zone cell lymphoma. Molecular detection of MYD88 p.L265P hotspot mutation supports the diagnosis of lymphoplasmacytic lymphoma since it is seen in about 90% of such lymphoma, which is much higher than other B-cell lymphomas. MYD88 p.L265P is a gain-of-function mutation that enhances the activity of the NF-κB signaling pathway and therefore drives lymphomagenesis. Other mutations in MYD88 are rarely reported. This study aims to report an unusual MYD88 in-frame deletion in an aggressive lymphoplasmacytic neoplasm. This is an IgM-positive, CD5- and CD10-negative mature B-cell lymphoma with prominent plasmacytic differentiation and aggressive features. The clinical and pathologic findings were most consistent with lymphoplasmacytic lymphoma. Next-generation sequencing identified an unusual MYD88 in-frame deletion in the absence of the hotpot p.L265P mutation. Other concurrent pathogenic mutations also include truncating mutations of TRAF3, which is a negative regulator of the NF-κB signaling pathway, and a missense mutation of TP53. Karyotype analysis showed complex karyotypes, including chromosome 6q deletion. By searching literature and online cancer databases, we identified only 8 other mature B-cell lymphomas with MYD88 in-frame deletions, but none of them was diagnosed with lymphoplasmacytic lymphoma. Recognizing such in-frame deletions is necessary to help understand the mutational spectrum of MYD88 in B-cell lymphomas. It remains to be further investigated whether such MYD88 in-frame deletions are also overrepresented in lymphoplasmacytic lymphoma among other B-cell lymphomas.
Asunto(s)
Linfoma de Células B de la Zona Marginal , Macroglobulinemia de Waldenström , Humanos , Factor 88 de Diferenciación Mieloide/genética , Factor 3 Asociado a Receptor de TNF/genética , FN-kappa B/genética , Mutación , Linfoma de Células B de la Zona Marginal/patología , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/patología , Cariotipo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVES: We assessed the utility of red blood cell (RBC) CD105 and side scatter (SSC) parameters by flow cytometry for the detection of low-grade myelodysplastic neoplasms (MDS) in bone marrow specimens. METHODS: Ten RBC parameters incorporating CD105 or SSC combined with the Meyerson-Alayed scoring system (MASS) metrics were retrospectively evaluated by flow cytometry for utility in detecting low-grade MDS (n = 56) compared with cytopenic controls (n = 86). RESULTS: Myelodysplastic neoplasms were associated with 7 of the RBC parameters in univariate analysis. Multivariate analysis using cutoff values based on optimal and 95% specificity levels of the RBC metrics and the MASS parameters revealed the SSC ratio of CD105-positive and CD105-negative RBC fractions (CD105+/- SSC); the percentage and coefficient of variation of the CD105-positive fraction of RBCs (CD105%, CD105+CV) emerged as significant RBC variables. Two simple scoring schemes using these RBC values along with MASS parameters were identified: 1 using CD105+/- SSC, CD105%, and CD105+CV combined with the percentage of CD177-positive granulocytes (CD177%), myeloblast percentage (CD34%), and granulocyte SSC (GranSSC), and the other incorporating CD105+/- SSC, CD105+CV, CD177%, CD34%, GranSSC, and B-cell progenitor percentage. Both demonstrated a sensitivity of approximately 80%, with a specificity of roughly 90% for the detection of MDS compared with cytopenic controls. CONCLUSIONS: The red blood cell parameter, CD105+/- SSC, appears to be beneficial in the evaluation of low-grade MDS by flow cytometry.
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Endoglina , Citometría de Flujo , Síndromes Mielodisplásicos , Humanos , Anciano , Femenino , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/patología , Persona de Mediana Edad , Masculino , Anciano de 80 o más Años , Adulto , Endoglina/metabolismo , Endoglina/sangre , Estudios Retrospectivos , Eritrocitos/patología , Antígenos CD/metabolismo , Adulto JovenRESUMEN
We identified 11 patients with CD10(+) cutaneous T-cell lymphoma by flow cytometry. All cases were CD4(+) and CD8(-). Three patients had extensive lymphadenopathy, systemic symptoms and an aggressive clinical course consistent with angioimmunoblastic T-cell lymphoma or peripheral T-cell lymphoma. However, 8 of the 11 patients had a prolonged disease course with gross morphology, histology and tumor cell phenotype indistinguishable from mycosis fungoides or Sezary syndrome. Immunohistochemical studies confirmed CD10 expression in seven of the eight cases and revealed the lymphoma cells were Bcl-6(+), PD-1(+), and EBV(-). Two had significant expression of CXCL-13(+). The findings indicate that lymphoma cells from mycosis fungoides or Sezary syndrome may express follicular center helper T-cell markers CD10, Bcl-6, and PD-1 and occasionally CXCL-13. The expression of these markers in some cases of mycosis fungoides/Sezary syndrome suggests follicular center helper T-cell differentiation and may lead to confusion in distinguishing mycosis fungoides/Sezary syndrome from other follicular center helper T-cell marker positive T-cell lymphomas with cutaneous manifestations.
Asunto(s)
Biomarcadores de Tumor/inmunología , Micosis Fungoide/inmunología , Síndrome de Sézary/inmunología , Neoplasias Cutáneas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Micosis Fungoide/patología , Síndrome de Sézary/patología , Neoplasias Cutáneas/patología , Linfocitos T Colaboradores-Inductores/patologíaRESUMEN
Transplantation of CD34⺠hematopoietic reconstituting cells (HRC) is an important treatment modality. The cells needed for clinical hematopoietic reconstitution after myeloablation most commonly derive from bone marrow which have been mobilized into the peripheral blood. The number of CD34⺠cells in mobilized blood samples is used to indicate the appropriateness of transplantation although it does not evaluate the two necessary functions for successful transplantation: long-term reconstitution mediated by cells with self-renewing proliferation and short-term hematopoietic differentiation mediated by progenitor cells. Using a novel high-resolution immunophenotyping technology on a flow cytometric platform, we have assessed uniformly mobilized CD34⺠cells for expression levels of 16 molecules previously associated with HRC function and sought correlations of these expression data with functional short-term assays for colony formation that do predict successful transplantation. We found that colony-forming units were significantly correlated with HoxB4 expression, which was explained by the number of CD34⺠cells in the samples. However, analysis of colony-forming units normalized to the CD34⺠cell count revealed a significant negative correlation with HoxB4 expression. Thus, increased levels of HoxB4 enhance CD34⺠cell number via self-renewing expansion but concomitantly depreciate the capacity for short-term differentiation per cell. Our findings demonstrate the translation of experimental findings into a clinical setting and suggest that the expression level of HoxB4 in CD34⺠cells can be used as a measure of a sample's appropriateness for transplantation.