Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia.
Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia.
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DOI：
10.3389/fonc.2018.00129
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发表时间：
2018
影响因子：
4.7
通讯作者：
Castilla LH
中科院分区：
文献类型：
--
作者：
Pulikkan JA;Castilla LH
急性髓系白血病(AML)是一组具有特定驱动基因突变的血液系统恶性肿瘤，这些突变直接导致了疾病的病理。在转化的早期阶段了解这些突变的起源和功能对于了解疾病的病因和设计有效的治疗方法至关重要。染色体倒位inv(16)被认为是造血干细胞(HSC)的始创性突变，产生白血病前期HSC(preL-HSCs)并伴有髓系偏向和分化障碍，并易患AML。在小鼠和人急性髓细胞白血病细胞中的研究已经建立了inv(16)急性髓系白血病遵循克隆进化模型，在该模型中，表达融合蛋白CBFβ-SMMHC的preL-HSC在骨髓中持续无症状。新出现的白血病启动细胞(LIC)由inv(16)和一组异质性突变组成。本文就目前对inv(16)白血病前期发展的认识，以及β-SMMHC与白血病前期进展和LIC活性相关的功能作一综述。我们还讨论了inv(16)AML病因学中的重要开放机制问题。
Acute myeloid leukemia (AML) is a collection of hematologic malignancies with specific driver mutations that direct the pathology of the disease. The understanding of the origin and function of these mutations at early stages of transformation is critical to understand the etiology of the disease and for the design of effective therapies. The chromosome inversion inv(16) is thought to arise as a founding mutation in a hematopoietic stem cell (HSC) to produce preleukemic HSCs (preL-HSCs) with myeloid bias and differentiation block, and predisposed to AML. Studies in mice and human AML cells have established that inv(16) AML follows a clonal evolution model, in which preL-HSCs expressing the fusion protein CBFβ–SMMHC persist asymptomatic in the bone marrow. The emerging leukemia-initiating cells (LICs) are composed by the inv(16) and a heterogeneous set of mutations. In this review, we will discuss the current understanding of inv(16) preleukemia development, and the function of CBFβ–SMMHC related to preleukemia progression and LIC activity. We also discuss important open mechanistic questions in the etiology of inv(16) AML.
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影响因子：
30.8
作者：
Faber ZJ;Chen X;Gedman AL;Boggs K;Cheng J;Ma J;Radtke I;Chao JR;Walsh MP;Song G;Andersson AK;Dang J;Dong L;Liu Y;Huether R;Cai Z;Mulder H;Wu G;Edmonson M;Rusch M;Qu C;Li Y;Vadodaria B;Wang J;Hedlund E;Cao X;Yergeau D;Nakitandwe J;Pounds SB;Shurtleff S;Fulton RS;Fulton LL;Easton J;Parganas E;Pui CH;Rubnitz JE;Ding L;Mardis ER;Wilson RK;Gruber TA;Mullighan CG;Schlenk RF;Paschka P;Döhner K;Döhner H;Bullinger L;Zhang J;Klco JM;Downing JR
通讯作者：
Downing JR
影响因子：
11.4
作者：
D'Costa, J;Chaudhuri, S;Friedman, AD
通讯作者：
Friedman, AD
影响因子：
5.3
作者：
Durst, KL;Lutterbach, B;Hiebert, SW
通讯作者：
Hiebert, SW
影响因子：
11.2
作者：
Farrar JE;Schuback HL;Ries RE;Wai D;Hampton OA;Trevino LR;Alonzo TA;Guidry Auvil JM;Davidsen TM;Gesuwan P;Hermida L;Muzny DM;Dewal N;Rustagi N;Lewis LR;Gamis AS;Wheeler DA;Smith MA;Gerhard DS;Meshinchi S
通讯作者：
Meshinchi S
影响因子：
5.4
作者：
KAMACHI, Y;OGAWA, E;SHIGESADA, K
通讯作者：
SHIGESADA, K