Blood：JAK2ex13Del驱动致癌转化，与慢性嗜酸性白血病和真性红细胞增多症相关

2019-10-15 QQY MedSci原创

JAK2的JH2区域的V617F突变是几种骨髓增生性肿瘤(MPNs)的致癌驱动因素，包括原发性血小板增多症、骨髓纤维化和真性红细胞增多症(PV)。在MPNs中也发现了JAK2的其他图标，最显著的是真性红细胞增多症中的12号外显子突变。现研究人员报到了一个新的复发性突变，在JAK2的JH2结构域中，缺失了4个氨基酸，并插入了一个可变氨基酸（Leu583-Ala586DelInsSer/Gln/Pro

JAK2的JH2区域的V617F突变是几种骨髓增生性肿瘤(MPNs)的致癌驱动因素，包括原发性血小板增多症、骨髓纤维化和真性红细胞增多症(PV)。在MPNs中也发现了JAK2的其他图标，最显著的是真性红细胞增多症中的12号外显子突变。

现研究人员报到了一个新的复发性突变，在JAK2的JH2结构域中，缺失了4个氨基酸，并插入了一个可变氨基酸（Leu583-Ala586DelInsSer/Gln/Pro）。所有4位携带该突变的患者均罹患嗜酸性粒细胞增多症，而且两位携带Leu583-Ala586DelInsSer突变的患者还符合PV和慢性嗜酸性粒细胞白血病（CEL）的诊断标准。

计算和功能性研究表明Leu583-Ala586DelInsSer（简称JAK2^ex13InDel）可通过一个类似于JAK2^V617F的机制下调JAK2，激活STAT5和ERK，并将亲本Ba/F3细胞转化为生长因子独立性。与JAK2^V617F相反， JAK2^ex13InDel 不需要外源性同型二聚体1型细胞因子受体来转化Ba/F3细胞，并可在缺乏配体的情况下激活β常链家族细胞因子受体（IL-3R、IL-5R、粒细胞集落刺激因子受体）信号，与嗜酸性粒细胞的临床表型一致。

认识到这种新的PV/CEL重叠型MPN具有重要的临床意义，因为PV和CEL患者都具有高血栓形成风险，可能需要同时减少红细胞、中性粒细胞和嗜酸性粒细胞的数量来预防血栓栓塞事件。对原因不明的嗜酸性粒细胞增多症患者的髓系恶性肿瘤中反复突变的基因进行二代靶向测序或可揭示更多的Leu583-Ala586DelInsSer/Gln/Pro病例，从而促进完善这种特殊MPN的表征。

原始出处：

Ami B Patel， et al.JAK2ex13InDeldrives oncogenic transformation and is associated with chronic eosinophilic leukemia and polycythemia vera.Blood.2019001385.https：//doi.org/10.1182/blood.2019001385

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2019-11-19 肉我只吃一口

#JAK#

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2019-10-17 kord1982

#红细胞#

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2019-10-17 ms9833124466084992

#3D#

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2019-10-17 jambiya

#致癌#

41 0
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2019-10-17 gao_jian4220

#JAK2#

42 0
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2019-10-17 linlin2317

#红细胞增多症#

0 0

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