Identification Of Anln As Etv6 Partner Gene In Recurrent T(7;12)(p15;p13): A Possible Role Of Deregulated Anln Expression In Leukemogenesis.

The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms. A recurrent ETV6 translocation, previously described in patients with acute myeloid leukemia (AML) (Genes Chromosomes Cancer 51:328-337,2012, Leuk Res 35:e212-214, 2011), whose partner has not been identified is t(7;12)(p15;p13). We herein report that the t(7;12)(p15;p13) fuses ETV6 to ANLN, a gene not previously implicated in the pathogenesis of hematological malignancies, and we demonstrate that this translocation leads to high expression of the fusion transcript in the myeloid and lymphoid lineages.1419

MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

Abstract\ud \ud \ud \ud Background\ud Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC.\ud \ud \ud \ud Methods\ud MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment.\ud \ud \ud \ud Results\ud Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression.\ud \ud \ud \ud Conclusions\ud Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.Financial support was provided by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP (05/51467-0 and 09/04166-5) and Albert Einstein Research and Education Institute – IIEP (IEP.PE.08-0125). CC and JR were funded by The Wellcome Trust. The authors acknowledge Dr. Flavio Borges for statistical analysis of miRNA expression and clinical data. The authors acknowledge the contribution of the GENCAPO (Brazilian Head and Neck Genome Project) for sample collection, clinical and pathological data collection and interpretation, and fruitful discussions (complete list of members and affiliations presented at http://www.gencapo.famerp.br)

The role of Wiskott Aldrich syndrome protein (WASP) in the chronic myeloid leukemia.

Bcr-Abl é a tirosina quinase (TK) responsável por causar a Leucemia Mielóide Crônica (LMC). Os últimos estudos de follow-up mostram que apenas 50% dos pacientes tratados com a segunda geração de inibidores de TK atinge a remissão completa, o que significa que metade desses pacientes necessita de um algo melhor do que está disponível. Wiskott Aldrich Syndrome Protein (WASP) é um gene essencial para o bom desenvolvimento e função das células hematopoiéticas. Ante esse contexto, decidimos investigar se WASP poderia ter algum papel ou relevância na LMC. Em conclusão, Bcr-Abl suprime a expressão WASP por um mecanismo epigenético. A re-expressão de WASP torna as células mais suscetíveis à apoptose em resposta ao Imatinib. Sugerimos que a recuperação da expressão WASP deve ser discutida como estratégia para a terapia da LMC.Bcr-Abl is the tyrosine kinase (TK) responsible for causing Chronic Myeloid Leukemia (CML). This fusion protein up- and down-regulates several genes and pathways, producing a strong resistance to apoptosis and a blockage of cell maturation in the hematopoietic compartment. The last follow-up studies provided that only 50% of the patients treated with second generation achieve complete remission, what means that one-half of these patients needs something better. Wiskott Aldrich Syndrome Protein (WASP) is an essential gene for the proper development and function of the hematopoietic cells. In the light of this background, we decided to investigate if WASP could have some role or relevance in the CML context. In conclusion, Bcr-Abl suppresses WASP expression by an epigenetic mechanism. The re-expression of WASP makes the CML cells more susceptible to apoptosis and contribute to respond to Imatinib. We suggest that recovery of WASP expression should be discussed as a new and additional strategy for CML therapy

The role of Wiskott Aldrich syndrome protein (WASP) in the chronic myeloid leukemia.

Bcr-Abl é a tirosina quinase (TK) responsável por causar a Leucemia Mielóide Crônica (LMC). Os últimos estudos de follow-up mostram que apenas 50% dos pacientes tratados com a segunda geração de inibidores de TK atinge a remissão completa, o que significa que metade desses pacientes necessita de um algo melhor do que está disponível. Wiskott Aldrich Syndrome Protein (WASP) é um gene essencial para o bom desenvolvimento e função das células hematopoiéticas. Ante esse contexto, decidimos investigar se WASP poderia ter algum papel ou relevância na LMC. Em conclusão, Bcr-Abl suprime a expressão WASP por um mecanismo epigenético. A re-expressão de WASP torna as células mais suscetíveis à apoptose em resposta ao Imatinib. Sugerimos que a recuperação da expressão WASP deve ser discutida como estratégia para a terapia da LMC.Bcr-Abl is the tyrosine kinase (TK) responsible for causing Chronic Myeloid Leukemia (CML). This fusion protein up- and down-regulates several genes and pathways, producing a strong resistance to apoptosis and a blockage of cell maturation in the hematopoietic compartment. The last follow-up studies provided that only 50% of the patients treated with second generation achieve complete remission, what means that one-half of these patients needs something better. Wiskott Aldrich Syndrome Protein (WASP) is an essential gene for the proper development and function of the hematopoietic cells. In the light of this background, we decided to investigate if WASP could have some role or relevance in the CML context. In conclusion, Bcr-Abl suppresses WASP expression by an epigenetic mechanism. The re-expression of WASP makes the CML cells more susceptible to apoptosis and contribute to respond to Imatinib. We suggest that recovery of WASP expression should be discussed as a new and additional strategy for CML therapy

A Novel Mechanism Of Npm1 Cytoplasmic Localization In Acute Myeloid Leukemia: The Recurrent Gene Fusion Npm1â haus1

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Correlation between flow cytometry and histologic findings: ten year experience in the investigation of lymphoproliferative diseases

Objective: To demonstrate the advantages of correlatingflow cytometry immunophenotyping with the pathology/immunohistochemistry of lymph nodes or nodules in the diagnosisof lymphoproliferative diseases. Methods: A retrospective studywas carried out of 157 biopsy or fine-needle aspiration lymph nodes/nodule specimens taken from 142 patients, from 1999 and 2009.The specimens were simultaneously studied with flow cytometryand pathology at Hospital Israelita Albert Einstein. The specimenswere prepared in hematoxylin/eosin, Giemsa, or monoclonal antibodystained slides for detecting specific antibodies for the purposesof pathology/immunohistochemical analysis. The samples werehemolyzed and marked with different monoclonal antibody panels fordifferent antigens in flow cytometry immunophenotyping. Results:The diagnostic results of pathology/immunohistochemical studiesand flow cytometry immunophenotyping agreed in 115 patients(81%), corresponding to 127 specimens, as follows according tothe pathologic diagnosis: 63 patients with non-Hodgkin’s B-celllymphoma; 26 patients with reactive lymphoid hyperplasia; 5 patientswith non-Hodgkin’s T-cell lymphoma; 4 patients with atypical lymphoidproliferation; 5 patients with a chronic granulomatous inflammatoryprocess; 5 patients with a non-hematologic diagnosis; 2 patientswith granulocytic sarcoma; 2 patients with thymoma; 1 patientwith byphenotypic leukemia; 1 patient with kappa plasmocytoma;1 patient with Hodgkin’s lymphoma. Subtypes of lymphomas couldbe classified by associating the two techniques: 19 patients withfollicular lymphoma; 15 patients with diffuse large B-cell lymphoma; 7patients with small lymphocytic B-cell lymphoma/chronic lymphocyticleukemia; 3 patients with mantle cell lymphoma; 1 patient withBurkitt’s lymphoma; 1 patient with MALT type lymphoma; 1 patientwith post-transplant lymphoproliferative disease; 2 patients with highgrade non-Hodgkin’s B-cell lymphoma; 1 patient with low grade non-Hodgkin’s B-cell lymphoma not otherwise specified; 1 patient withHodgkin’s lymphoma; and 12 patients with B-cell non-Hodgkin’slymphoma not otherwise specified. Conclusion: Flow cytometryadds to the results of morphologic and immunohistochemical studies,facilitating a rapid and accurate diagnosis of lymphoproliferativediseases