Braf mutations in Hairy Cell Leukemia
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This study identified BRAF mutations in patients with hairy cell leukemia (HCL). The BRAF V600E mutation was present in all HCL patients tested, leading to overactive BRAF signaling and increased cell proliferation. Immunohistological and Western Blot tests found constitutive activation of the RAF-MEK-ERK pathway in HCL cells. A BRAF inhibitor reduced phosphorylation of MEK and ERK, indicating BRAF drives HCL pathogenesis. Identifying this genetic mutation improves understanding of HCL and could inform future treatment development.
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Alternative splicing by kk sahu
Introduction
What RNA Splicing???
Discovery
Types
Alternative Splicing
Mechanism
Regulatory element And protein
Splicing repression
Splicing activation
Significance
Diseases
Conclusion
Refrences
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Braf mutations in Hairy Cell Leukemia
- 1. BRAF MUTATIONS IN HAIRY CELL LEUKEMIAEnrico Tiacci, Vladmir Trinof, Gianluca Schiavoni, Antony Holmes, Wolfgang Kern, Maria Paola Martelli, et al. Jenniffer Correa Gutierrez Daniela Castaño Correa Molecular Biology Universidad Pontificia Bolivariana 2011
- 2. Introduction Leukemia Acute or chronic neoplastic disease of the bone marrow. Unrestrained proliferation of white blood cells. Anemia, impaired blood clotting, and enlargement of the lymph nodes, liver, and spleen.
- 4. Spreads to the lymph nodes.
- 10. Amino Acid substitution of glutamic acid for valine at position 600 of BRAF protein.V600E mutation
- 13. Relationship of RAF with HCL This pathology is caused by a mutation on the BRAF protein kinase which normally travels to the nucleus to control the cell functions. In HCL, the BRAF protein prevents helps cancer development.
- 16. Main Objective To identify genetic mutations on hairy cells through massive parallel sequencing of patients with hairy cell leukemia.
- 17. Métodos Muestras: 47 pacientes con presentacionclinica y morfologica de HCL. Positivosparaannexin A 1: analisisimmunohistolgico. Coexistencia de CD11c, CD25 y CD103 en citometria de flujo, o ambos.
- 18. Métodos Muestras de sangreperiferica de pacienteíndice. Secuencial de exomas en celulasleucemicaspurificadas CD19- positivas: tiempo de latencia de la enfermedad (>90%). Secuencial de exomas en celulasleucemicaspurificadas CD19- negativasmononucleadas: quimioterapia.
- 19. Métodos Consensoinformado: analisisgenético. Protocoloaprovadopor el comité de la Universidad de Perugia. Otrospacientes: consensoinformado oral.
- 20. Métodos Secuencial de exoma: Seleccion de regionesquecodifican en un genomahumanaparaidentificar genes asociados con desordenespococomunes. Exomassecuenciales: Se encontraronmutaciones somaticas en los candidatospormedio de Genome Analyzer IIx (Illumina).
- 21. Métodos PCR: polymerase-chain-reaction Amplificacionenzimaticain vitro directa de un gen o un fragmento de DNA o indirecta de RNA. Desnaturalizacion del DNA paradarhebrassencillas. Hibridacionespecifica: primer. Replicacion: DNA polimerasa. Rastreo de mutaciones.
- 22. Métodos Inmunofluorescencia: Determina proteinas y hormonas. El fluorocromo es una sustancia queabsorbeluz (200-400nm). Emite luz (400-700nm).
- 23. Métodos Western Blot Variación de transferencia southern. SDS- PAGE poliacrilámida gel electroforesis. SDS : detergente con carga (-) Incubación con anticuerpos. Determina proteína.
- 24. Resultados
- 25. Resultados
- 26. Resultados Pruebasinmunohistologicas y Western Blot: Celulas HCL expresaronfosforilacion de MEK y ERK. Activacionconstitutiva de RAF-MEK-ERK, mediante la via protein-kinasa en HCL activadapormitogeno. El PLX-4720 es un inhibidorespecifico del BRAF activoquemarcaunadisminucion en la fosforilacion de ERK y MEK.
- 27. Resultados
- 28. Discussion
- 29. Secuencial
- 30. Conclusions The study of molecular biology laboratory techniques has helped identify the characteristics of cells that are specific to a disease. The BRAF V600E mutation was present in all patients with HCL, which can lead in the future to a greater understanding of this pathology.
- 31. Conclusions This study can incite scientists to research an effective treatment for patients with HCL. Knowledge of this gene can lead to future early prevention of HCL and other kinds of leukemia.
- 32. Jenniffer Correa
- 33. Daniela Castaño
- 34. Bibliography WebMD. Leukemia - Topic Overview. [ August 3, 2011]. [Internet]; Available on: http://www.webmd.com/cancer/tc/leukemia-topic-overview Bio Oncology. What is BRAF? [ August 3, 2011]. [Internet]; Available on: http://www.biooncology.com/research-education/braf/braf/in dex.ht ml Martinez S LM. BiologíaMolecular. Ed 6. Medellin. 2011. Pg 113, 131, 143.
- 35. THANK YOU!
Editor's Notes
- BRAF protein is an important intermediary for the RAS-RAF signaling. Preclinical studies demonstrate that mutations in the BRAF gene allow for BRAF to signal independently of upstream cues. As a result, mutated BRAF causes overactive downstream signaling via MEK and ERK. MEK: mitogen activated protein.