c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish.
c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish.
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c-myb 过度活跃会导致斑马鱼出现骨髓和淋巴恶性肿瘤。
DOI：
10.1038/leu.2016.170
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发表时间：
2017-01
期刊：
影响因子：
11.4
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Liu W;Wu M;Huang Z;Lian J;Chen J;Wang T;Leung AY;Liao Y;Zhang Z;Liu Q;Yen K;Lin S;Zon LI;Wen Z;Zhang Y;Zhang W
c-MYB转录因子是造血细胞增殖和分化的关键调节因子，c-MYB活性失调通常与各种血液疾病相关。然而，由于缺乏合适的动物模型，其致病作用仍然很大程度上未知。在这里，我们报告了具有 c-Myb 过度活性（称为 c-mybhyper）的 c-myb-gfp 转基因斑马鱼的详细特征。该细胞系从胚胎期到成年期表现出异常的粒细胞扩张，类似于人类骨髓增生异常综合征（MDS）。引人注目的是，随着年龄的增长，一小部分 c-mybhyper 成鱼会出现急性髓细胞白血病样或急性淋巴白血病样疾病。 c-mybhyper成鱼的骨髓和淋巴恶性肿瘤可能是由c-myb过度活跃引起的，导致许多细胞周期相关基因失调和造血前体细胞过度增殖。最后，用c-myb靶向药物flavopiridol治疗可以缓解c-mybhyper胚胎和成鱼的MDS样症状。我们的研究建立了斑马鱼模型，用于研究 c-Myb 相关白血病发生的细胞和分子机制以及抗白血病药物筛选。
The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-mybhyper). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood. Strikingly, a small portion of c-mybhyper adult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-mybhyper adult fish are likely caused by the hyperactivity of c-myb, resulting in the dysregulation of a number of cell-cycle-related genes and hyperproliferation of hematopoietic precursor cells. Finally, treatment with c-myb target drug flavopiridol can relieve the MDS-like symptoms in both c-mybhyper embryos and adult fish. Our study establishes a zebrafish model for studying the cellular and molecular mechanisms underlying c-Myb-associated leukemogenesis as well as for anti-leukemic drug screening.
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影响因子：
2.7
作者：
Karp JE;Blackford A;Smith BD;Alino K;Seung AH;Bolaños-Meade J;Greer JM;Carraway HE;Gore SD;Jones RJ;Levis MJ;McDevitt MA;Doyle LA;Wright JJ
通讯作者：
Wright JJ
影响因子：
2.7
作者：
GOPAL, V;HULETTE, B;PREISLER, H
通讯作者：
PREISLER, H
影响因子：
11.4
作者：
Murati, A.;Gervais, C.;Birnbaum, D.
通讯作者：
Birnbaum, D.
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
2.6
作者：
Liu, F;Wen, ZL
通讯作者：
Wen, ZL