Ahmadzadeh Ahmad, Shahrabi Saeid, Jaseb Kaveh, Norozi Fatemeh, Shahjahani Mohammad, Vosoughi Tina, Hajizamani Saeideh, Saki Najmaldin
Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences , Ahvaz.
Department of Biochemistry and Hematology, Semnan University of Medical Sciences , Semnan, Iran.
Oncol Rev. 2014 Sep 23;8(2):253. doi: 10.4081/oncol.2014.253.
BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK) signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL). BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.
BRAF是一种丝氨酸/苏氨酸激酶，在丝裂原活化蛋白激酶（MAPK）信号通路中起调节作用。RAF基因的突变，尤其是BRAF蛋白的突变，会导致该级联反应的刺激增加，从而引起细胞的失控分裂和恶性肿瘤的发展。在包括毛细胞白血病（HCL）在内的多种人类恶性肿瘤中，已观察到该蛋白编码基因的几种突变。BRAF V600E是BRAF第15外显子中报道的最常见突变，几乎在所有经典HCL病例中都能观察到，但在包括HCL变异型在内的其他B细胞恶性肿瘤中呈阴性。因此，它可作为区分这些B细胞疾病的标志物。我们还讨论了HCL中微小RNA（miRNA）与信号通路（包括MAPK）之间的相互作用。当存在这种突变时，使用BRAF蛋白抑制剂可能是一种有效的治疗方法。在这篇综述中，我们评估了BRAF基因突变在HCL发病机制和进展中的作用。
