RESUMO
Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders. The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in all malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.
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Neoplasias Hematológicas , Hematologia , Aberrações Cromossômicas , Análise Citogenética/métodos , Citogenética , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Humanos , Cariótipo , Prognóstico , Sociedades MédicasRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n = 222) to receive standard chemotherapy ("3 + 7") with or without lenalidomide at a dose of 20 mg/day 1-21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without lenalidomide (20 mg/day 1-21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Lenalidomida/administração & dosagem , Leucemia Mieloide Aguda/patologia , Masculino , Síndromes Mielodisplásicas/patologia , Prognóstico , Indução de Remissão , Taxa de SobrevidaRESUMO
OBJECTIVES: CML, PV, ET and PMF are so called classical MPN with distinct clinical phenotypes. The discovery of the BCR-ABL1 translocation and mutations in driver genes JAK2, MPL and CALR has provided novel insights in their pathogenesis. While these mutations are thought to be mutually exclusive, rare cases of MPN with coexisting driver mutations have been reported. However, little is known about the clinical, biological and molecular characteristics of these patients and the interaction of the neoplastic clones. METHODS: We retrospectively studied 11 MPN patients with coexisting driver mutations (JAK2 V617F + BCR-ABL1: n = 8; CALR type 2 + BCR-ABL1: n = 1; JAK2 V617F + MPL W515: n = 1; JAK2 V617F + CALR type 1: n = 1). To assess possible associated molecular aberrations, we analysed DNA of six patients using NGS. RESULTS: In four CML patients, decreasing BCR-ABL1 transcript levels with increasing JAK2 V617F allele burden under TKI were observed. This strongly suggests that the coexistence of driver mutations originates from two different clones growing independently. Additional somatic mutations were detected in 5 out of 6 (83%) patients affecting 4 different genes, confirming the heterogeneity of this study cohort. Suboptimal response to TKI was observed with a higher frequency (4/8 patients) than reported in conventional series of CML and the overall tolerance of treatment with hydroxyurea and/or imatinib in our series was poor. CONCLUSION: Given the emergence of NGS in clinical practice, more similar cases will be identified in the coming years. The optimal treatment strategy for this rare group of patients is uncertain and toxicity of combination treatment may have to be considered.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hematológicas/genética , Mutação , Transtornos Mieloproliferativos/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Hidroxiureia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/tratamento farmacológicoRESUMO
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients.
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Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Deleção Cromossômica , Cromossomos Humanos Par 1 , Mieloma Múltiplo/genética , Proteínas Ribossômicas/genética , Proteínas de Ligação a DNA/genética , Genes Supressores de Tumor , Humanos , Proteína do Locus do Complexo MDS1 e EVI1 , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mutação , Proto-Oncogenes/genética , RNA Mensageiro/análise , Fatores de Transcrição/genéticaRESUMO
Although post-transplant lymphoproliferative disorder is a classical complication encountered after kidney transplantation, its diagnosis can still be challenging and its outcome life-threatening. Most cases are related to Epstein-Barr virus (EBV) infection and occur mainly in the first year post-transplant, favoured by the seronegative EBV status of the recipient transplanted with a kidney from a seropositive donor, and strong immunosuppression. We report the case of a young kidney-pancreas transplant recipient who developed post-transplant lymphoproliferative disorder (PTLD) early after transplantation, with a rapid fatal issue. We review the pathogenesis, clinical presentation, and management of PTLD with a focus on prevention.
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Infecções por Vírus Epstein-Barr , Imunossupressores/efeitos adversos , Transplante de Rim , Transtornos Linfoproliferativos , Transplante de Pâncreas , Complicações Pós-Operatórias , Adulto , Diabetes Mellitus Tipo 1/complicações , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/fisiopatologia , Evolução Fatal , Feminino , Humanos , Imunossupressores/administração & dosagem , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/fisiopatologia , Transtornos Linfoproliferativos/terapia , Transplante de Pâncreas/efeitos adversos , Transplante de Pâncreas/métodos , Tomografia por Emissão de Pósitrons/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapiaRESUMO
We report on a 75-year-old woman who presented with recurrent episodes of hypotension, anasarca, renal failure, hypoalbuminaemia without proteinuria, suggestive of systemic capillary leak syndrome (SCLS). Further investigations led to a diagnosis of diffuse large B-cell lymphoma. Secondary SCLS associated with non-Hodgkin lymphoma is reviewed.
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Síndrome de Vazamento Capilar/complicações , Síndrome de Vazamento Capilar/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/etiologia , Idoso , Síndrome de Vazamento Capilar/terapia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapiaRESUMO
BACKGROUND: Multicentric Castleman's disease (MCD) is a rare, non-clonal lymphoproliferative disorder characterized by constitutional symptoms, anaemia and generalised lymphadenopathy. Its incidence among the HIV-positive population seems to have increased during the past decades. AIM: The present study intends to compare demographic features, clinical presentation, laboratory studies, imaging results as well as treatment regimens and outcome in our MCD patients to those of larger reported series. METHOD: We reviewed the files of 920 HIV-1-infected patients from our AIDS Reference Centre. Data was collected from the operating software for the patients' medical records of our institution (Medical Explorer v3r3, Cliniques St Luc, 2008). RESULTS: We report a series of four cases of MCD among our HIV/AIDS patients' cohort. Three were of African origin. They were diagnosed after 2003, after a mean duration of 54 months of HIV-seropositivity (ranging from 7 to 120 months) All presented with characteristic clinical features and laboratory findings, and were started on HAART a few months before or upon MCD diagnosis. Three patients were treated with chemotherapy (ABV), and one with HAART only. One patient who was given ABV is in continuous remission after 3 years of follow-up. The remaining three are alive, with good symptom control, regardless of the treatment they received. CONCLUSION: MCD is a rare, but rising issue among HIV-infected patients. The clinical and paraclinical features of our series of four patients are in keeping with those of larger reported series. Currently, treatment is mainly chemotherapy-based, but a wide variety of protocols have been used, mainly because of the lack of available evidence. New approaches such as anti-CD 20 antibodies seem highly effective, and the role of HHV-8 needs to be further investigated, as it might be an important target for future treatment. In light of this review, we are looking forward to offer these opportunities to our patients, despite unhelpful regulations.
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Hiperplasia do Linfonodo Gigante/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Terapia Antirretroviral de Alta Atividade , Hiperplasia do Linfonodo Gigante/microbiologia , Hiperplasia do Linfonodo Gigante/patologia , Comorbidade , Feminino , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 8 , Humanos , Imuno-Histoquímica , Linfonodos/virologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Fatores de Risco , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/patologia , Tomografia Computadorizada por Raios XAssuntos
Leucemia Linfocítica Crônica de Células B/genética , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative neoplasm characterized by the FIP1L1-PDGFRA fusion gene, variant PDGFRA fusions or other genetic lesions. Most FIP1L1-PDGFRA positive patients enjoy durable and complete molecular responses to low-dose imatinib (Glivec/Gleevec). However, resistance mediated by a T674I mutation in the ATP-binding pocket of PDGFRA has been reported in advanced disease, and sorafenib, a potent inhibitor of RAF-1, B-RAF, VEGFR and PDGFR, is active against this mutant in vitro. We describe a case of FIP1L1-PDGFRalpha T674I CEL in blast crisis that responded to sorafenib (Nexavar). However, this clinical response was short-lived because of the rapid emergence of a FIP1L1-PDGFRalpha D842V mutant. An N-Nitroso-N-ethylurea-mutagenesis screen indeed identified this mutant as a major sorafenib-resistant mutant. In vitro, the novel FIP1L1-PDGFRalpha D842V mutant is highly resistant to sorafenib, imatinib, dasatinib (Sprycell) and PKC412 (Midostaurin). Thus, sorafenib is clinically active in imatinib-resistant FIP1L1-PDGFRalpha T674I CEL, but the rapid emergence of other mutants may limit the response duration. The identification of new PDGFR inhibitors will be required to overcome resistance by this D842V mutant.
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Benzenossulfonatos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/genética , Mutação/genética , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Idoso , Animais , Crise Blástica , Western Blotting , Células Cultivadas , Doença Crônica , Humanos , Síndrome Hipereosinofílica/metabolismo , Masculino , Camundongos , Niacinamida/análogos & derivados , Compostos de Fenilureia , Fosforilação/efeitos dos fármacos , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/efeitos dos fármacos , Células Precursoras de Linfócitos B/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Terapia de Salvação , SorafenibeAssuntos
Fator de Transcrição MafB/análise , Mieloma Múltiplo/diagnóstico , Translocação Genética , Biomarcadores Tumorais , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 20 , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Proteínas Oncogênicas/análise , PrognósticoRESUMO
Episomes with the NUP214-ABL1 fusion gene have been observed in 6% of T-ALL. In this multicentric study we collected 27 cases of NUP214-ABL1-positive T-ALL. Median age was 15 years with male predominance. Outcome was poor in 12 patients. An associated abnormality involving TLX1 or TLX3 was found in all investigated cases. Fluorescent in situ hybridization revealed a heterogeneous pattern of NUP214-ABL1 amplification. Multiple episomes carrying the fusion were detected in 24 patients. Episomes were observed in a significant number of nuclei in 18 cases, but in only 1-5% of nuclei in 6. In addition, intrachromosomal amplification (small hsr) was identified either as the only change or in association with episomes in four cases and two T-ALL cell lines (PEER and ALL-SIL). One case showed insertion of apparently non-amplified NUP214-ABL1 sequences at 14q12. The amplified sequences were analyzed using array-based CGH.These findings confirm that the NUP214-ABL1 gene requires amplification for oncogenicity; it is part of a multistep process of leukemogenesis; and it can be a late event present only in subpopulations. Data also provide in vivo evidence for a model of episome formation, amplification and optional reintegration into the genome. Implications for the use of kinase inhibitors are discussed.
Assuntos
Amplificação de Genes , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas de Fusão Oncogênica/genética , Adolescente , Adulto , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Proteínas de Homeodomínio/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/etiologia , Masculino , Pessoa de Meia-Idade , Plasmídeos , Proteínas Proto-Oncogênicas/genética , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Deleção Cromossômica , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação , Translocação GenéticaRESUMO
Chromosomal translocations represent an important prognostic indicator in B-cell chronic lymphocytic leukemia (B-CLL). However, their value had been neither determined in homogeneously treated patients nor compared to that of IgV(H) mutational status. Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgV(H) and of TP53 mutational status before treatment with 2-chloro-2'-deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of the patients, including both balanced (n=12) and unbalanced (n=33) types. IgV(H) was mutated in 43% of the patients. Patients with translocations were more heavily pretreated (P=0.05), presented with more complex karyotypes (P<0.001), 17p abnormalities and TP53 mutations, and had a higher failure rate (59 vs 21% in patients without translocations, P=0.004). Patients with unbalanced translocations displayed a shorter median treatment-free survival (TFS, 6.9 vs 35.9 months, log rank 22.72, P<0.001) and overall survival (OS, 13.0 vs 68.0 months, log rank 16.51, P<0.001), as compared to patients without translocation. In multivariate analysis, unbalanced translocations were independently associated with therapeutic failure, short TFS and short OS. IgV(H) mutational status was independently associated with risk of failure and TFS, but not OS. In B-CLL patients treated with CdA, translocations are strong predictors of outcome.
Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 17/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Falha de Tratamento , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.
Assuntos
Leucemia de Células B/genética , Linfoma de Células B/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética , Adulto , Idoso , Proteína 3 do Linfoma de Células B , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 19 , Análise Citogenética , Feminino , Rearranjo Gênico , Genes de Imunoglobulinas , Histocitoquímica , Humanos , Hibridização in Situ Fluorescente , Leucemia de Células B/classificação , Leucemia de Células B/patologia , Linfoma de Células B/classificação , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
For long, T-cell acute lymphoblastic leukemia (T-ALL) remained in the shadow of precursor B-ALL because it was more seldom, and showed a normal karyotype in more than 50% of cases. The last decennia, intense research has been carried out on different fronts. On one side, development of normal thymocyte and its regulation mechanisms have been studied in multiple mouse models and subsequently validated. On the other side, molecular cytogenetics (fluorescence in situ hybridization) and mutation analysis revealed cytogenetically cryptic aberrations in almost all cases of T-ALL. Also, expression microarray analysis disclosed gene expression signatures that recapitulate specific stages of thymocyte development. Investigations are still very much actual, fed by the discovery of new genetic aberrations. In this review, we present a summary of the current cytogenetic changes associated with T-ALL. The genes deregulated by translocations or mutations appear to encode proteins that are also implicated in T-cell development, which prompted us to review the 'normal' and 'leukemogenic' functions of these transcription regulators. To conclude, we show that the paradigm of multistep leukemogenesis is very much applicable to T-ALL and that the different genetic insults collaborate to maintain self-renewal capacity, and induce proliferation and differentiation arrest of T-lymphoblasts. They also open perspectives for targeted therapies.
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Leucemia-Linfoma de Células T do Adulto/genética , Linfócitos/patologia , Timo/patologia , Linhagem da Célula , Aberrações Cromossômicas , Genes Homeobox , Humanos , Leucemia-Linfoma de Células T do Adulto/enzimologia , Leucemia-Linfoma de Células T do Adulto/patologia , Proteínas Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de SinaisRESUMO
The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.
Assuntos
Linfoma Difuso de Grandes Células B/genética , Proteínas Repressoras/genética , Translocação Genética , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 3 , Feminino , Fatores de Transcrição Forkhead , Regulação Neoplásica da Expressão Gênica , Rearranjo Gênico , Humanos , Linfoma de Células B/genética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.
Assuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 6 , Leucemia Linfocítica Crônica de Células B/genética , Translocação Genética , Humanos , Hibridização in Situ Fluorescente , CariotipagemRESUMO
OBJECTIVES: Follicular lymphoma (FL) is the most common adult non-Hodgkin's lymphoma. Diagnosis is based on morphology and can be confirmed by cytogenetic, flow cytometry (FCM) or molecular studies. Despite all these complementary approaches, diagnosis sometimes remains difficult. The purpose of the present work was to characterise the expression of new specific follicular cells markers which allows us to target specifically the abnormal FL cell population in FCM. METHODS: A total of 153 samples from healthy subjects and from patients with chronic B-cell lymphoproliferative disorders were analysed by FCM in the same conditions for purpose of comparison. RESULTS: We showed that CD44 is weakly expressed in FL cells compared with peripheral blood mononuclear cell from normal blood donors and others cells from B lymphoproliferative diseases. We nevertheless observed bone marrow samples where some immature B-cell population express CD44 with lower fluorescence intensity. Therefore, we developed a double antibody combination, using CD44 and CD38, which allowed us to separate the normal immature cells from the pathological population using FCM. CONCLUSION: This new phenotypic approach offers an accurate (sensitivity and specificity of 93% and 96%, respectively), fast and low sample consuming method for the diagnosis of FL.