德國弗賴堡大學(xué)醫(yī)院１７日發(fā)表公報說，該院研究人員發(fā)現(xiàn)了導(dǎo)致幼年型粒—單核細(xì)胞白血病的可遺傳性基因變異,。這一成果有助于對各種白血病成因及療法的研究,。
幼年型粒—單核細(xì)胞白血病是一種罕見的惡性血癌,，多發(fā)于幼兒。該院兒童與青少年醫(yī)學(xué)中心的研究人員首先發(fā)現(xiàn),，在１５％患兒的血液中,，一種名為ＣＢＬ的基因出現(xiàn)變異；他們隨后又發(fā)現(xiàn),，所有患兒家長體內(nèi)都有ＣＢＬ突變,，其中５０％出現(xiàn)在家長的精子或卵子細(xì)胞中，另外５０％出現(xiàn)在身體的其他器官中,。
研究人員說,，由于許多患兒有語言學(xué)習(xí)障礙、發(fā)育不良,、弱聽和隱睪等癥狀,，他們認(rèn)為，ＣＢＬ基因的正常表達(dá)對眾多器官的發(fā)育都非常重要,。
研究人員表示,，這一成果將有助于對各種白血病成因及其療法的進(jìn)一步研究。此外,，導(dǎo)致患兒白細(xì)胞增多的信號傳導(dǎo)問題也出現(xiàn)在其他一些癌癥中,，因此這一研究成果對提高癌癥治療水平具有普遍意義。
這一成果發(fā)表在最新一期《自然—基因?qū)W》上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Genetics doi:10.1038/ng.641
Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia
Charlotte M Niemeyer1,18, Michelle W Kang2,18, Danielle H Shin2,18, Ingrid Furlan1, Miriam Erlacher1, Nancy J Bunin3, Severa Bunda4, Jerry Z Finklestein5, Kathleen M Sakamoto6, Thomas A Gorr1, Parinda Mehta7, Irene Schmid8, Gabriele Kropshofer9, Selim Corbacioglu10, Peter J Lang11, Christoph Klein12, Paul-Gerhard Schlegel13, Andrea Heinzmann1, Michaela Schneider1, Jan Stary14, Marry M van den Heuvel-Eibrink15, Henrik Hasle16, Franco Locatelli17, Debbie Sakai2, Sophie Archambeault2, Leslie Chen2, Ryan C Russell4, Stephanie S Sybingco4, Michael Ohh4, Benjamin S Braun2, Christian Flotho1 & Mignon L Loh2
CBL encodes a member of the Cbl family of proteins, which functions as an E3 ubiquitin ligase. We describe a dominant developmental disorder resulting from germline missense CBL mutations, which is characterized by impaired growth, developmental delay, cryptorchidism and a predisposition to juvenile myelomonocytic leukemia (JMML). Some individuals experienced spontaneous regression of their JMML but developed vasculitis later in life. Importantly, JMML specimens from affected children show loss of the normal CBL allele through acquired isodisomy. Consistent with these genetic data, the common p.371Y>H altered Cbl protein induces cytokine-independent growth and constitutive phosphorylation of ERK, AKT and S6 only in hematopoietic cells in which normal Cbl expression is reduced by RNA interference. We conclude that germline CBL mutations have developmental, tumorigenic and functional consequences that resemble disorders that are caused by hyperactive Ras/Raf/MEK/ERK signaling and include neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome and Legius syndrome.
