PHF6 Mutations in Hematologic Malignancies.
PHF6 Mutations in Hematologic Malignancies.
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DOI：
10.3389/fonc.2021.704471
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发表时间：
2021
影响因子：
4.7
通讯作者：
Weinberg OK
中科院分区：
文献类型：
--
作者：
Kurzer JH;Weinberg OK
下一代测序已经在恶性血液病中发现了几个与突变相关的基因，这些基因可以作为疾病的潜在生物标记物。因此，在血液学领域，了解这些基因是至关重要的。本综述重点介绍PHF6，一种高度保守的表观遗传转录调节因子，对神经发育和造血起重要作用。PHF6是一种肿瘤抑制蛋白，其突变和缺失通常与T淋巴细胞白血病的发生有关，而在急性髓系白血病和其他髓系肿瘤中较少发生。PHF6失活似乎是T淋巴细胞白血病发生的早期事件，需要协同作用，包括NOTCH1突变或TLX1和TLX3的过度表达，以促进疾病的全面发展。相比之下，PHF6突变往往发生在髓系恶性肿瘤中较晚，经常伴随RUNX1突变，并且往往与疾病进展有关。此外，PHF6似乎在血液系统恶性肿瘤的谱系可塑性中发挥作用，PHF6突变通常出现在混合表型急性白血病中，并倾向于T谱系标记的表达。由于相互矛盾的数据，PHF6突变的预后意义尚不清楚，部分研究表明，与野生型PHF6的恶性肿瘤相比，结果没有显著差异，其他研究表明，某些PHF6突变患者的预后较差。未来有必要阐明PHF6在T淋巴母细胞白血病的发生、髓系恶性肿瘤的进展中所起的作用，以及它在血液系统肿瘤中的整体预后意义。
Next generation sequencing has uncovered several genes with associated mutations in hematologic malignancies that can serve as potential biomarkers of disease. Keeping abreast of these genes is therefore of paramount importance in the field of hematology. This review focuses on PHF6, a highly conserved epigenetic transcriptional regulator that is important for neurodevelopment and hematopoiesis. PHF6 serves as a tumor suppressor protein, with PHF6 mutations and deletions often implicated in the development of T-lymphoblastic leukemia and less frequently in acute myeloid leukemia and other myeloid neoplasms. PHF6 inactivation appears to be an early event in T-lymphoblastic leukemogenesis, requiring cooperating events, including NOTCH1 mutations or overexpression of TLX1 and TLX3 for full disease development. In contrast, PHF6 mutations tend to occur later in myeloid malignancies, are frequently accompanied by RUNX1 mutations, and are often associated with disease progression. Moreover, PHF6 appears to play a role in lineage plasticity within hematopoietic malignancies, with PHF6 mutations commonly present in mixed phenotype acute leukemias with a predilection for T-lineage marker expression. Due to conflicting data, the prognostic significance of PHF6 mutations remains unclear, with a subset of studies showing no significant difference in outcomes compared to malignancies with wild-type PHF6, and other studies showing inferior outcomes in certain patients with mutated PHF6. Future studies are necessary to elucidate the role PHF6 plays in development of T-lymphoblastic leukemia, progression of myeloid malignancies, and its overall prognostic significance in hematopoietic neoplasms.
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影响因子：
11.4
作者：
通讯作者：
--
成人 T 细胞急性淋巴细胞白血病中 PHF6 和 NOTCH1 突变共存。
影响因子：
2.9
作者：
Li M;Xiao L;Xu J;Zhang R;Guo J;Olson J;Wu Y;Li J;Song C;Ge Z
通讯作者：
Ge Z
影响因子：
4.6
作者：
Chang YH;Yu CH;Jou ST;Lin CY;Lin KH;Lu MY;Wu KH;Chang HH;Lin DT;Lin SW;Chen HY;Yang YL
通讯作者：
Yang YL
影响因子：
3.2
作者：
Chao, Mwe Mwe;Todd, Matthew A.;Kontny, Udo;Neas, Katherine;Sullivan, Michael J.;Hunter, Alasdair G.;Picketts, David J.;Kratz, Christian P.
通讯作者：
Kratz, Christian P.
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI