Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia
Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia
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DOI：
10.1182/blood-2006-04-018259
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发表时间：
2006-10-01
期刊：
影响因子：
20.3
通讯作者：
Green, Anthony R.
中科院分区：
文献类型：
--
作者：
Scott, Linda M.;Scott, Mike A.;Green, Anthony R.
获得性V617F JAK2突变发生在真性红细胞增多症(PV)或原发性血小板增多症(ET)患者中。在一定比例的V617F阳性患者中，有丝分裂重组产生突变纯合子细胞，随着时间的推移，这些细胞逐渐占据主导地位。然而，纯合子的流行情况尚不清楚，因为以前的报告研究了野生型、V617F杂合子和V617F纯合子突变细胞的混合群体。因此，我们分析了34例PV或ET患者的1766个单个血细胞集落，其中粒细胞测序显示突变峰不占优势。PV患者中V617F阳性的红细胞破裂单位(BFU-ES)的发生率明显高于ET患者(P=0.022)，且17例PV患者中均检出V617F纯合子的BFU-ES，而ET患者中无一例检出V617F纯合子的BFU-ES(P<0.01)。此外，2例ET患者经多核细胞转化后出现突变纯合子细胞。这些结果表明，V617F纯合子红系祖细胞在大多数PV患者中都存在，但在ET患者中很少发生。
An acquired V617F JAK2 mutation occurs in patients with polycythemia vera (PV) or essential thrombocythemia (ET). In a proportion of V617F-positive patients, mitotic recombination produces mutation-homozygous cells that come to predominate with time. However, the prevalence of homozygosity is unclear, as previous reports studied mixed populations of wild-type, V617F-heterozygous, and V617F-homozygous mutant cells. We therefore analyzed 1766 individual hematopoletic colonies from 34 patients with PV or ET in whom granulocyte sequencing demonstrated that the mutant peak did not predominate. V617F-positive erythroid burst-forming units (BFU-Es) were more frequent in patients with PV compared with patients with ET (P = .022) and, strikingly, V617F-homozygous BFU-Es were detected in all 17 patients with PV, but in none of the patients with ET (P < .001). Moreover, mutation-homozygous cells were present in 2 patients with ET after polycythemic transformation. These results demonstrate that V617F-homozygous erythroid progenitors are present in most patients with PV but occur rarely in those with ET.