骨髓增殖性肿瘤伴骨纤巨核细胞形态及BCR-ABL、JAK2V617F基因的相关性研究

Correlation study of BCR-ABL, JAK-2 and the morphology of the bone marrow megakaryocytes in myeloproliferative neoplasms with myelofibrosis

目的探讨和了解骨髓巨核细胞异形性改变在CML、ET、PV伴骨髓纤维组织增生中的诊断意义,分析BCR-ABL融合基因和JAK2V617突变对巨核细胞形态的影响及临床意义。方法收集山西医科大学第二临床医学院2009年1月至2012年8月诊治的CML、ET、PV患者的外周血常规检查和骨髓活检切片资料并进行回顾性分析,将骨髓巨核细胞形态分为七类,分别为Ⅰ型(单个核型)、Ⅱ型(多个核型)、Ⅲ型(多分叶型)、Ⅳ型(分叶不好型)、Ⅴ型(大核小核型)、Ⅵ型(巨核细胞簇)、Ⅶ型(骨小梁旁型)。观察骨髓切片中巨核细胞,通过卡方检验方法分析CML融合基因B3a2、B2a2,ET、PVJAK2V617F突变对巨核细胞形态影响的差异。结果各组巨核细胞均伴异形性改变,CMLB3a2-1与B3a2-0、ETJAK2V617F(-)-1与JAK2V617F(-)-0、PV组巨核细胞差异无统计学意义(P>0.05)。骨小梁旁巨核细胞在ETJAK2V617F(+)-1与JAK2V617F(+)-0组有统计学差异(P=0.000)、巨核细胞簇分别在CMLB2a2-1与B2a2-0组、ETJAK2V617F(+)-1与JAK2V617F(+)-0组有统计学差异(P=0.024,0.030)。结论 CML-B2a2型、ET、PV中JAK2V617F突变伴骨髓纤维组织率高。巨核细胞簇和骨小梁旁巨核细胞、巨核细胞簇分别对B2a2、JAK2V617F突变伴骨纤程度轻微时有一定的早期诊断意义。

[ Abstract ] Objective To evaluate the morphologic features of CML, ET and PV with hyperplasia of fibrous tissue and their influence on bone marrow megakaryocytes in patients with BCR-ABL fusion gene and JAK2V617 mutation. Methods We retrospectively examined the diagnosis and treatment of CML, ET and PV with hyperplasia of fibrous tissue in our hospital from January 2009 to August 2012. Patients were divided into 7 groups according the types of morphologic features： type I （ single karyotype ）, type II （ multiple karyotypes）, type IU （multiple split leaf type）, type 1V （split leaves with poor prognosis）, V （ big nuclear small nuclear karyotype）, type VI （cluster）, VII （trabecular side type）. Z2 test was used to evaluate the influence of fusion gene subtypes （B3a2, B2a2）, ET, PV and JAK2V617 mutations on morphological differences of megakaryocytes. Results The megakaryocytes were morphologically different among the groups. B3a2-1 group and B3a2-0 group were morphologically similar. JAK2V617F （-）-I, JAK2V617F （-）-0 of ET and PV groups were morphologically similar. For patients with cluster of megakaryocytes there was statistically difference between B2a2-1 and B2a2-0.For patients with trabecular side megakaryocyte there was statistically difference between JAK2V617F （＋） -1, JAK2V617F （＋） -0 of ET （P 〈 0.05） and JAK2V617F （＋） -1 and JAK2V617F （＋） -0 of ET （P = 0.024, 0.030）. Conclusions Incidence of myelofibrosis was higher in patients with fusion gene B2a2. Mgakaryocyte cell cluster is a good indicator of disease in patients with B2a2 and slight hyperplasia of fibrous tissue. In patients with JAK2V617 mutations of ET and PV, trabecular side type and cluster are helpful for early diagnosis.