RESUMO
Plasmablastic lymphoma is an uncommon aggressive non-Hodgkin B-cell lymphoma type defined as a high-grade large B-cell neoplasm with plasma cell phenotype. Genetic alterations in MYC have been found in a proportion (~60%) of plasmablastic lymphoma cases and lead to MYC-protein overexpression. Here, we performed a genetic and expression profile of 36 plasmablastic lymphoma cases and demonstrate that MYC overexpression is not restricted to MYC-translocated (46%) or MYC-amplified cases (11%). Furthermore, we demonstrate that recurrent somatic mutations in PRDM1 are found in 50% of plasmablastic lymphoma cases (8 of 16 cases evaluated). These mutations target critical functional domains (PR motif, proline rich domain, acidic region, and DNA-binding Zn-finger domain) involved in the regulation of different targets such as MYC. Furthermore, these mutations are found frequently in association with MYC translocations (5 out of 9, 56% of cases with MYC translocations were PRDM1-mutated), but not restricted to those cases, and lead to expression of an impaired PRDM1/Blimp1α protein. Our data suggest that PRDM1 mutations in plasmablastic lymphoma do not impair terminal B-cell differentiation, but contribute to the oncogenicity of MYC, usually disregulated by MYC translocation or MYC amplification. In conclusion, aberrant coexpression of MYC and PRDM1/Blimp1α owing to genetic changes is responsible for the phenotype of plasmablastic lymphoma cases.
Assuntos
Variação Genética , Linfoma Plasmablástico/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por HIV/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Linfoma Plasmablástico/complicações , Linfoma Plasmablástico/patologiaRESUMO
This prospective multi-institutional phase II study was designed to assess the efficacy and safety of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphomas. Eighty-one patients diagnosed with diffuse large B-cell lymphoma (DLBCL, n = 68), primary mediastinal DLBCL (n = 6) and follicular lymphoma Grade 3b (n = 7), with an age-adjusted International Prognostic Index >1, were eligible for analysis. Median age was 60 years (range: 21-77). Sixty-five patients (80·2%) achieved complete response. After a median follow-up time of 64 months, 10-year event-free survival and overall survival (OS) were 47·8% and 63·6%, respectively. None of the studied clinical and biological characteristics were associated with poorer outcome. Interestingly, patients with BCL6 rearrangement achieved a 10-year OS of 100%, while patients with BCL2 rearrangement exhibited a poorer outcome compared to activated B-cell tumours and germinal centre B-cell without BCL2 rearranged tumours. Results achieved with DA-EPOCH-R showed a good long-term outcome and a tolerable toxicity profile in high-risk large B cell lymphoma patients. Outcome was not affected by tumour cell proliferation or by cell of origin, highlighting the requirement of new biological markers for patient subclassification of high-risk DLBCL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Rituximab , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto JovemRESUMO
AIMS: Here we report two cases of follicular lymphoma that transformed to CD30 positive diffuse large B cell lymphoma and review the literature on this topic. RESULTS: The first case represents an example of early transformation of conventional low-grade follicular lymphoma to CD30-positive large B cell lymphoma. Immunoglobulin (Ig)H and cytogenetic identity was demonstrated between both components. High-dose and auto-stem cell transplant (SCT) was applied and complete response was achieved. The second case represents an example of d'emblee transformation of intrafollicular neoplasia to CD30-positive large B cell lymphoma. Immunoglobulin K deleting element (IgKde) and cytogenetic identity between both phases was demonstrated. The patient was in partial response after four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). CONCLUSIONS: CD30 expression was found to be associated in these cases to the transformation event and could be considered a therapeutic target to add to conventional immunochemotherapeutic regimens, even in combination with auto-SCT. We suggest looking for CD30 expression in transformed follicular lymphoma cases.
Assuntos
Transformação Celular Neoplásica/patologia , Antígeno Ki-1/metabolismo , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica/metabolismo , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
AIMS: CD30-positive primary cutaneous lymphoproliferative disorders include several entities with differing clinical presentation but overlapping histological features, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (C-ALCL). DUSP22-IRF4 locus translocation is present in 20-57% of C-ALCLs, and has also been described in a series of 11 lymphomatoid papulosis patients, where it was associated with a particular biphasic histological pattern, including pagetoid reticulosis-type epidermal infiltration. We aimed to study whether the presence of this translocation may define distinctive histological features in C-ALCL. METHODS AND RESULTS: We collected three cases of C-ALCL with histological features similar to those described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement. We studied their histological features and immunophenotype, using a panel of antibodies against CD30, TCR-ßF1, TCR-γ, CD4, CD8, CD20, Ki-67 and ALK. FISH analyses were performed using an IRF4-DUSP22 break-apart probe for the study of the 6p25.3 rearrangement. FISH results were positive in the three cases, which all showed distinctive histological and immunohistochemical features: a diffuse dermal infiltrate of atypical medium-to-large cells, and marked epidermotrophism with small, atypical intra-epidermal lymphocytes. CONCLUSIONS: Our findings suggest that the presence of 6p25.3 rearrangement might be related to this particular biphasic pattern.
Assuntos
Cromossomos Humanos Par 6/genética , Rearranjo Gênico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/genética , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/etiologia , Lectina de Ligação a Manose/genética , Lectinas de Ligação a Manose/genética , Adulto , Idoso , Feminino , Genótipo , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante AutólogoAssuntos
Ciclina D3/genética , Ciclina D3/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Mutação , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma de Células B/patologia , Neoplasias Esplênicas/patologiaRESUMO
AIMS: Immunoglobulin light-chain expression is used routinely as an indirect marker of clonality for recognizing B cell lymphoproliferative disorders. METHODS AND RESULTS: Here we describe four floral follicular hyperplasia cases in the gastrointestinal tract (appendix and rectum) of children (4 to 6 years). Immunohistochemical studies revealed lambda light-chain restriction that was associated with polyclonal IgH pattern. Clinical features and follow-up of the patients did not reveal any other systemic symptoms, laboratory abnormalities or organ alterations. CONCLUSIONS: Recognition of this phenomenon is useful in the diagnosis of nodular lymphoid hyperplasia of the gastrointestinal tract, for avoiding overdiagnosis of lymphoid malignancies, and raises concerns that the identification of light-chain restriction is not necessarily a marker of monoclonality.
Assuntos
Apêndice/patologia , Cadeias Leves de Imunoglobulina , Transtornos Linfoproliferativos/patologia , Reto/patologia , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia/imunologia , Hiperplasia/patologia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Transtornos Linfoproliferativos/imunologia , Masculino , Reação em Cadeia da Polimerase MultiplexAssuntos
Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfonodos/metabolismo , Linfonodos/patologia , Receptor Notch1/genética , Ativação Transcricional , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/mortalidade , Mutação , Taxa de Mutação , Fosfoproteínas/genética , Prognóstico , Fatores de Processamento de RNA , Receptor Notch1/metabolismo , Ribonucleoproteína Nuclear Pequena U2/genéticaRESUMO
Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse. The pattern of mutations suggest that the 2 tumors might have evolved from a common progenitor clone with MYD88L265P being the founder mutation. A meta-analysis of the literature shows a significantly high frequency of concurrent MYD88L265P and CD79B ITAM mutations in primary CNS lymphoma and testicular DLBCL, underscoring the role of B cell receptor and nuclear factor kB activation by somatic mutations in these lymphomas that colonize immune-privileged sites. In summary, here we illustrate that targeted next generation sequencing for the detection of hot spot somatic mutations in relapsed DLBCL is useful to confirm ABC phenotype and discovers relevant information that might influence therapeutic decision.
Assuntos
Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/genética , Evolução Clonal/genética , Linfoma Difuso de Grandes Células B/genética , Fator 88 de Diferenciação Mieloide/genética , Recidiva Local de Neoplasia/genética , Glândulas Suprarrenais/patologia , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , NF-kappa B/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismo , Lobo Temporal/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/secundárioAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Risco Ajustado/métodos , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/classificação , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Transplante de Células-Tronco/métodos , Vincristina/administração & dosagem , Adulto JovemRESUMO
STUDY DESIGN: A randomized, double-blind, placebo-controlled study, with a six-month follow-up period. OBJECTIVES: The aim of this study was to test the hypothesis that a 72-hour dose of subanesthetic ketamine in this surgical procedure reduces postoperative morphine use and to assess whether there are fewer adverse effects, if postoperative recovery is faster, if there is less peri-incisional hyperalgesia, or if there is lower incidence of persistent postsurgical pain. SUMMARY OF BACKGROUND DATA: Tissue injury and high opioid requirements following posterior spinal fusion surgery produce central sensitization, which can in turn be associated with hyperalgesia and chronic pain. Clinical trials involving this type of procedure using subanesthetic ketamine doses have assessed pain and morphine requirements with contradictory results. The effects of prolonged subanesthetic ketamine doses on postoperative recovery, mechanical hyperalgesia, and the incidence of chronic pain are unknown. METHODS: A total of 48 pediatric patients between 10 and 18 years diagnosed with idiopathic scoliosis were randomized to receive perioperative low-dose ketamine or placebo for 72âhours. They received general anesthesia, intraoperative remifentanil, and morphine postoperatively (patient-controlled analgesia). We measured morphine consumption, pain at rest and during movement (coughing), undesirable effects, and sedation during morphine treatment. The onset of oral intake, ambulation, and hospital stay were recorded. The extent of the peri-incisional hyperalgesia was measured at 72âhours and pain controls were conducted postsurgery. RESULTS: Primary endpoint results (total cumulative morphine consumption while admitted) were obtained in 44 patients. Results were 2.72 (SD 1.13) in the placebo group and 3.13 (SD 1.13) in the study group (Pâ=â0.2903), with no significant differences. Moreover, differences were not found between the experimental group and the placebo group in the secondary endpoints analyzed. CONCLUSION: Our findings do not support the routine combining of prolonged subanesthetic ketamine doses with opioids in posterior fusion surgery in children with idiopathic scoliosis. LEVEL OF EVIDENCE: 2.
Assuntos
Ketamina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Escoliose/cirurgia , Analgesia Controlada pelo Paciente/métodos , Criança , Método Duplo-Cego , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Medição da Dor/métodos , Piperidinas/uso terapêutico , Remifentanil , Fatores de TempoRESUMO
Follicular lymphoma in situ (FLIS) and mantle cell lymphoma in situ (MCLIS) are histopathologic findings of undetermined clinical significance. We studied a series of 341 consecutive lymph node resection specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma between 1998 and 2000. Incidental and isolated FLIS was identified in 11/341 patients (3.23%), whereas incidental and isolated MCLIS was found in 2/341 patients (0.59%). None of these cases developed overt lymphoma. A second series of 17 cases of FLIS (16 cases) and MCLIS (1 case) from consultation files was analyzed. Five cases with incidental and isolated FLIS were identified. None of these cases developed overt lymphoma. Overall, none of the 16 cases with incidental and isolated FLIS in both series developed overt FL after a median follow-up of 54 months (range, 7 to 187 mo). However, 12 of these cases with a clinical suspicion of lymphoproliferative disorder showed the association (in different lymph nodes) or combination (in the same sample) of FLIS or MCLIS with other lymphoid neoplasms (FL, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of FLIS and MCLIS seems to strictly depend on the clinical context. Incidental FLIS or MCLIS seem to have a very low risk for transformation, which recommends careful clinical examination after histopathologic diagnosis and conservative management with follow-up for a limited period of time.
Assuntos
Carcinoma in Situ/patologia , Achados Incidentais , Linfoma Folicular/patologia , Linfoma de Célula do Manto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/epidemiologia , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfoma Folicular/epidemiologia , Linfoma de Célula do Manto/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 17 , Hibridização in Situ Fluorescente , Síndromes Mielodisplásicas/genética , Proteína Supressora de Tumor p53/genética , Bandeamento Cromossômico , HumanosRESUMO
OBJECTIVES: To compare, from a biological and clinical perspective, a significant group of patients with AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) with another group of AML carrying different abnormalities of 3q at q21 or q26, the latter named as the AML abn(3q) group. METHODS: We developed a national survey with the participation of 13 Spanish hospitals, and retrospectively reviewed (from 1990 to 2010) these subtypes of AML. Fifty-five patients were collected: 35 with AML inv(3)/t(3;3) and 20 with AML abn(3q). A data collecting page that included main features at diagnosis, therapeutic approach and response, and survival variables, was distributed and completed. RESULTS: We did not find significant differences in sex, age, history of myelodysplastic syndrome or chemo-/radiotherapy, clinical presentation, WBC and platelet counts, hemoglobin level, blasts immunophenotype, serum lactatedehydrogenase, peripheral blood and bone marrow cellular dysplasia, and bone marrow biopsy findings. Although the association with monosomy 7 was significantly more frequent in AML inv(3)/t(3;3), this did not seem to influence outcome. The lack of response to the different modalities of treatment and the aggressive course of the disease were the standard in both cohorts of patients. DISCUSSION: Although not yet recognized by the World Health Organization classification, our results are in agreement with the findings of other authors, who include both subsets of AML together in the same group of adverse prognosis. CONCLUSION: In an attempt to simplify and bound entities with similar genetic background and clinical behavior, it would be desirable to bring together both subgroups of AML in a single section.
RESUMO
MYC is a transcription factor that regulates many critical genes for cell proliferation, differentiation, and biomass accumulation. MYC is one of the most prevalent oncogenes found to be altered in human cancer, being deregulated in about 50 % of tumors. Although MYC deregulation has been more frequently associated to lymphoma and lymphoblastic leukemia than to myeloid malignancies, a body of evidence has been gathered showing that MYC plays a relevant role in malignancies derived from the myeloid compartment. The myeloid leukemogenic activity of MYC has been demonstrated in different murine models. Not surprisingly, MYC has been found to be amplified or/and deregulated in the three major types of myeloid neoplasms: acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, including chronic myeloid leukemia. Here, we review the recent literature describing the involvement of MYC in myeloid tumors.
Assuntos
Genes myc/genética , Leucemia Mieloide/genética , Animais , Humanos , Síndromes Mielodisplásicas/genéticaRESUMO
Chromosomal abnormalities are detected in 40-60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (-7) or 7q deletion (7q-) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected -7/7q- in 5.2% of patients. Presence of -7/7q- was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of -7/7q- by CC.
Assuntos
Bandeamento Cromossômico , Cromossomos Humanos Par 7 , Hibridização in Situ Fluorescente/métodos , Monossomia , Síndromes Mielodisplásicas/genética , Mapeamento Cromossômico , Humanos , PrognósticoRESUMO
Bcl-6 is essential for germinal centre development and normal antibody responses, and has major roles in controlling B-cell proliferation and differentiation. Bcl-6 expression is tightly controlled, but neither the nature of all the regulatory signals nor their interactions are known. Bcl-6 expression is induced in Bcr-Abl expressing lymphoid cell lines by the tyrosine kinase inhibitor, imatinib. We show that p38 MAPK mediates induction of Bcl-6 following inhibition of Bcr-Abl by imatinib. Next we analyze p38 function in a germinal centre B-cell line, Ramos. p38 is phosphorylated under basal conditions, and studies with p38 inhibitors show that it induces Bcl-6 expression. Membrane bound CD40 ligand activates p38 but also other MAPK pathways that strongly repress Bcl-6 and the overall effect is reduction in Bcl-6 expression. Surprisingly soluble CD40 ligand induces Bcl-6 by activating p38 without activating the repressive pathways. Hence different types of CD40 signalling are associated with varying effects on Bcl-6 expression. Transcription reporter assays demonstrate p38 responsive sequences at about 4.5 kb from the transcription start site. Immunocytochemistry of tonsil sections show phosphorylated p38 in a minor population of germinal centre B-cells. We demonstrate for the first time that p38 induces Bcl-6 transcription, but increased protein expression occurs only when the strong pathways repressing Bcl-6 are not activated.
Assuntos
Antígenos CD40/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/genética , Receptores de Antígenos de Linfócitos B/fisiologia , Anticorpos Anti-Idiotípicos/farmacologia , Crise Blástica/genética , Crise Blástica/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Modelos Biológicos , Tonsila Palatina/efeitos dos fármacos , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Transdução de Sinais/fisiologiaRESUMO
MYC is a transcription factor that regulates many critical genes for cell proliferation, differentiation, and biomass accumulation. MYC is one of the most prevalent oncogenes found to be altered in human cancer, being deregulated in about 50 % of tumors. Although MYC deregulation has been more frequently associated to lymphoma and lymphoblastic leukemia than to myeloid malignancies, a body of evidence has been gathered showing that MYC plays a relevant role in malignancies derived from the myeloid compartment. The myeloid leukemogenic activity of MYC has been demonstrated in different murine models. Not surprisingly, MYC has been found to be amplified or/and deregulated in the three major types of myeloid neoplasms: acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, including chronic myeloid leukemia. Here, we review the recent literature describing the involvement of MYC in myeloid tumors (AU)