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1.
Diagn Pathol ; 18(1): 52, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37098615

RESUMEN

Breast-implant associated (BIA) lymphoma is an infrequent type of cancer occurring in the fluid and fibrous capsule around a textured breast implant. Recently, both the 2022 WHO 5th edition classification of Haematological tumours (WHO HAEM5) and 2022 International Consensus Classification of Mature Lymphoid Neoplasms (22ICC), recognized breast implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) as a definitive entity, defined as a mature CD30-positive T-cell lymphoma, confined by a fibrous capsule, in a breast implant setting. Only few B-cell lymphomas have been reported in the literature to be associated with breast implants. Here we report two EBV-positive Diffuse Large B-cell lymphomas (EBV + DLBCL) in relation to a breast implant, both expressing CD30 as well as EBV latency type 3. Both lesions were considered as DLBCL associated with chronic inflammation (CI-DLBCL), but one presented as a 7 cm solid mass, while the other presented as a fibrin-associated DLBCL (FA-DLBCL) in an HIV patient. Clinically, both are in complete remission 6 months or longer after capsulectomy and graft removal, without additional chemotherapy.Such cases, characterized by large CD30-positive cells, can easily be misdiagnosed as BIA-ALCL if the cell of origin is not further established. Therefore, a diagnostic panel including lineage-specific B-and T-cell markers and EBER in situ hybridization is essential to recognize this rare entity, to understand lymphomagenesis, to predict outcome and to define clinical approach.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Infecciones por VIH , Linfoma de Células B Grandes Difuso , Linfoma Anaplásico de Células Grandes , Humanos , Femenino , Implantes de Mama/efectos adversos , Herpesvirus Humano 4 , Antígeno Ki-1 , Neoplasias de la Mama/patología , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/etiología , Linfoma Anaplásico de Células Grandes/patología , Linfoma de Células B Grandes Difuso/diagnóstico
2.
Acta Clin Belg ; 76(5): 402-405, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32228367

RESUMEN

We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the face and larynx. After thorough biochemical investigations, an acquired deficiency of C1-INH was suspected. To evaluate a potential underlying malignancy, a whole-body FDG-PET/CT was performed and showed solely a marked splenomegaly pointing towards a splenic marginal zone lymphoma, which was confirmed by pathological examination.With this case, we discuss the pathophysiology, diagnosis and management of recurrent acquired angioedema attacks as the first presentation of an underlying lymphoproliferative disease.


Asunto(s)
Angioedema , Angioedemas Hereditarios , Anciano , Angioedema/diagnóstico , Angioedema/etiología , Femenino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones
3.
Acta Haematol ; 142(4): 197-207, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31163431

RESUMEN

OBJECTIVES: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with chronic myeloid leukaemia (CML). METHODS: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context) between May 2013 and May 2016. Data collection took place between October 2016 and February 2017. RESULTS: All 60 participants (69 interruptions/discontinuations) had chronic-phase CML and 75% had at least a major molecular response (≥MMR) at interruption/discontinuation. Most interruptions/discontinuations occurred while on imatinib (36/69; 49%) and dasatinib (20/69; 29%). Most interruptions/discontinuations occurred due to side effects/intolerance (46/69; 67%); other reasons included a wish to conceive (6/69; 9%) and attempts to achieve treatment-free remission (TFR) (6/69; 9%). Interruptions due to side effects occurred later for imatinib- or dasatinib-treated patients than for those on nilotinib or ponatinib. Treatment was re-initiated in 62% (43/69) of cases. Most interruptions caused by side effects/intolerance were followed by treatment changes. All 4 patients with ≥MR 4.5 at interruption/discontinuation and ≥11-month follow-up who had not restarted treatment maintained the response. CONCLUSION: Although TKIs are used for long-term CML treatment, physicians sometimes recommend interruptions/discontinuations. In this study, interruptions/discontinuations were mainly caused by side effects or intolerance, rather than TFR attempts.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Anciano , Bélgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
4.
Genes Chromosomes Cancer ; 55(5): 428-41, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26850007

RESUMEN

The recurrent 9p24.1 aberrations in lymphoid malignancies potentially involving four cancer-related and druggable genes (JAK2, CD274/PDL1, PDCD1LG2/PDL2, and KDM4C/JMJD2Cl) are incompletely characterized. To gain more insight into the anatomy of these abnormalities, at first we studied 9p24.1 alterations in 18 leukemia/lymphoma cases using cytogenetic and molecular techniques. The aberrations comprised structural (nine cases) and numerical (nine cases) alterations. The former lesions were heterogeneous but shared a common breakpoint region of 200 kb downstream of JAK2. The rearrangements predominantly targeted the PDL locus. We have identified five potential partner genes of PDL1/2: PHACTR4 (1p34), N4BP2 (4p14), EEF1A1 (6q13), JAK2 (9p24.1), and IGL (22q11). Interestingly, the cryptic JAK2-PDL1 rearrangement was generated by a microdeletion spanning the 3'JAK2-5'PDL1 region. JAK2 was additionally involved in a cytogenetically cryptic IGH-mediated t(9;14)(p24.1;q32) found in two patients. This rare but likely underestimated rearrangement highlights the essential role of JAK2 in B-cell neoplasms. Cases with amplification of 9p24.1 were diagnosed as primary mediastinal B-cell lymphoma (five cases) and T-cell lymphoma (four cases). The smallest amplified 9p24.1 region was restricted to the JAK2-PDL1/2-RANBP6 interval. In the next step, we screened 200 cases of classical Hodgkin lymphoma by interphase FISH and identified PDL1/2 rearrangement (CIITA- and IGH-negative) in four cases (2%), what is a novel finding. Forty (25%) cases revealed high level amplification of 9p24.1, including four cases with a selective amplification of PDL1/2. Altogether, the majority of 9p24.1 rearrangements occurring in lymphoid malignancies seem to target the programmed death-1 ligands, what potentiates the therapeutic activity of PD-1 blockade in these tumors. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Antígeno B7-H1/genética , Janus Quinasa 2/genética , Linfoma/genética , Mutación , Bandeo Cromosómico , Perfilación de la Expresión Génica , Humanos , Cariotipificación
5.
PLoS One ; 9(1): e85851, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24416450

RESUMEN

The transcription factor FOXP1 is implicated in the pathogenesis of B-cell lymphomas through chromosomal translocations involving either immunoglobulin heavy chain (IGH) locus or non-IG sequences. The former translocation, t(3;14)(p13;q32), results in dysregulated expression of FOXP1 juxtaposed with strong regulatory elements of IGH. Thus far, molecular consequences of rare non-IG aberrations of FOXP1 remain undetermined. Here, using molecular cytogenetics and molecular biology studies, we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas with no apparent structural aberrations of the gene. Our study revealed that non-IG rearrangements of FOXP1 are usually acquired during clinical course of various lymphoma subtypes, including diffuse large B cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukemia, and correlate with a poor prognosis. Importantly, these aberrations constantly target the coding region of FOXP1, promiscuously fusing with coding and non-coding gene sequences at various reciprocal breakpoints (2q36, 10q24 and 3q11). The non-IG rearrangements of FOXP1, however, do not generate functional chimeric genes but commonly disrupt the full-length FOXP1 transcript leading to an aberrant expression of N-truncated FOXP1 isoforms (FOXP1(NT)), as shown by QRT-PCR and Western blot analysis. In contrast, t(3;14)(p13;q32)/IGH-FOXP1 affects the 5' untranslated region of FOXP1 and results in overexpress the full-length FOXP1 protein (FOXP1(FL)). RNA-sequencing of a few lymphoma cases expressing FOXP1(NT) and FOXP1(FL) detected neither FOXP1-related fusions nor FOXP1 mutations. Further bioinformatic analysis of RNA-sequencing data retrieved a set of genes, which may comprise direct or non-direct targets of FOXP1(NT), potentially implicated in disease progression. In summary, our findings point to a dual mechanism through which FOXP1 is implicated in B-cell lymphomagenesis. We hypothesize that the primary t(3;14)(p13;q32)/IGH-FOXP1 activates expression of the FOXP1(FL) protein with potent oncogenic activity, whereas the secondary non-IG rearrangements of FOXP1 promote expression of the FOXP1(NT) proteins, likely driving progression of disease.


Asunto(s)
Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Linfoma de Células B/genética , Proteínas Represoras/genética , Rotura Cromosómica , Cromosomas Humanos Par 3/genética , Factores de Transcripción Forkhead/metabolismo , Redes Reguladoras de Genes/genética , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Cariotipificación , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Análisis de Secuencia de ARN
6.
Genes Chromosomes Cancer ; 52(10): 928-44, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23873701

RESUMEN

BMI1, a Polycomb-group gene located at 10p12.2, is implicated in the pathogenesis of a variety of tumors. However, the genetic molecular mechanisms underlying its aberrant expression in cancer cells remain largely unknown. In this study, we show that BMI1 is recurrently targeted by chromosomal aberrations in B-cell leukemia/lymphoma. We identified a novel t(10;14)(p12;q32)/IGH-BMI1 rearrangement and its IGL variant in six cases of chronic lymphocytic leukemia (CLL) and found that these aberrations were consistently acquired at time of disease progression and high grade transformation of leukemia (Richter syndrome). The IG-BMI1 translocations were not associated with any particular molecular subtype of CLL and the leukemias were negative for common mutations of NOTCH1 and TP53, known to increase a risk of progression and transformation in CLL. In addition, using FISH and SNP array analysis, we identified a wide range of BMI1-involving 10p12 lesions in 17 cases of mantle cell lymphoma (MCL). These aberrations included various balanced and unbalanced structural abnormalities and very frequently but not exclusively, were associated with gain of the BMI1 locus and loss of the 10p terminal sequences. These findings point to genomic instability at the 10p region in MCL which likely promotes rearrangements and deregulation of BMI1. Our findings are in line with previously published observations correlating overexpression of BMI1 with tumor progression and chemoresistance. In summary, our study provides new insights into genetic molecular mechanisms underlying aberrant expression of BMI1 in lymphoma and documents its contribution in the pathogenesis of Richter syndrome and MCL.


Asunto(s)
Aberraciones Cromosómicas , Leucemia Linfocítica Crónica de Células B/genética , Linfoma de Células B/genética , Complejo Represivo Polycomb 1/genética , Anciano , Anciano de 80 o más Años , Desequilibrio Alélico , Ciclina D1/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Translocación Genética
8.
Leuk Lymphoma ; 53(8): 1445-51, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22280536

RESUMEN

Aberrations of TP53 (mutations and/or deletions) are associated with a dismal prognosis in chronic lymphocytic leukemia (CLL). Complete loss of ATM is another mechanism of failed DNA damage response and also associated with poorer prognosis in CLL. However, p53 dysfunction may arise through alternative mechanisms unrelated to structural aberrations (deletion and/or mutation) of TP53 or ATM, and thus be undetectable by traditional DNA-directed approaches (fluorescence in situ hybridization [FISH], sequencing, karyotyping). In order to address the latter changes, and also to better understand the consequences of TP53/ATM aberrations, p53 functional assays have recently been developed. The purpose of dynamic assessment of p53 response in CLL is to carry out a comprehensive analysis of all mechanisms causing p53-deficient phenotype, including those unrelated to genomic aberrations of TP53 and ATM. The present review focuses on the current knowledge of p53 function assays in CLL, including important features such as technical issues, correlation with structural aberrations and clinical value.


Asunto(s)
Regulación Leucémica de la Expresión Génica , Genes p53 , Leucemia Linfocítica Crónica de Células B/genética , Proteína p53 Supresora de Tumor/genética , Citogenética , Daño del ADN , Eliminación de Gen , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , MicroARNs/genética , Fenotipo , Pronóstico
9.
Ann Hematol ; 91(6): 863-73, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22205151

RESUMEN

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.


Asunto(s)
Cromosomas Humanos Par 8 , Genes myc/genética , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Prolinfocítica/genética , Translocación Genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 8/genética , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/clasificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Prolinfocítica/clasificación , Leucemia Prolinfocítica/diagnóstico , Leucemia Prolinfocítica/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos
10.
Cancer Genet ; 204(8): 462-4, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21962897

RESUMEN

Here, we report the case of a 57-year-old man, who was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). His diagnostic workup identified a translocation t(3;9)(p13;p13). This is the fifth case reported to date that involved the forkhead box P1 gene (FOXP1) and paired box gene 5 (PAX5). The PAX5-FOXP1 translocation is a nonrandom aberration, which is recurrent in both childhood and in adult B-ALL, and may contribute to leukemogenesis by blocking differentiation of hematopoietic cells into mature B-cells.


Asunto(s)
Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 9/genética , Factores de Transcripción Forkhead/genética , Factor de Transcripción PAX5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Represoras/genética , Translocación Genética/genética , Linfocitos B/patología , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética
11.
Genes Chromosomes Cancer ; 49(11): 991-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20662075

RESUMEN

Interphase fluorescence in situ hybridization (FISH) detects nonrandom cytogenetic abnormalities in plasma cell (PC) dyscrasia according to PC burden. However, when performed on cultured whole bone marrow (BM), it often fails to detect these aberrations. We have compared this interphase FISH technique with FISH after PC purification or identification to detect recurrent aberrations. In this study, 235 BM samples were collected from patients with multiple myeloma (MM) or related PC disorders regardless of disease status. All samples were analyzed in parallel. Clonal abnormalities were detected in 34.9% of cultured samples compared with 71.0% PC selected samples (P < 0.001). Moreover, FISH on PCs allowed to detect more abnormalities per case (P < 0.001) and identified higher percentages of abnormal nuclei (P < 0.001). This study indicates that FISH on PCs is the preferred technique for routine cytogenetic investigation of MM.


Asunto(s)
Aberraciones Cromosómicas , Hibridación Fluorescente in Situ , Interfase , Paraproteinemias/genética , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Genes Chromosomes Cancer ; 48(10): 843-53, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19582829

RESUMEN

We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis (n = 172) or during disease evolution (n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B-cell mitogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin-2 (IL-2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL-2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL-2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL-2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q) (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL-2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques.


Asunto(s)
Aberraciones Cromosómicas , Citogenética/métodos , Interleucina-2/farmacología , Leucemia Linfocítica Crónica de Células B/genética , Oligonucleótidos/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Proliferación Celular/efectos de los fármacos , Bandeo Cromosómico , Interpretación Estadística de Datos , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación/métodos , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Translocación Genética , Células Tumorales Cultivadas
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