原发性骨髓纤维化早期患者骨髓形态学特征研究

The morphology features of bone marrow in the prefibrotic-early primary myelofibrosis

目的 比较原发性骨髓纤维化（PMF）早期患者与原发性血小板增多症（ET）患者骨髓细胞形态学特征,并探讨JAK2V617F突变对骨髓细胞形态的影响.方法 收集接受一般药物治疗并转化为纤维化明显期的7例PMF早期患者标本,分析其骨髓形态学特征.依据2008年WHO诊断标准,对2003年1月至2011年3月同步进行骨髓涂片、印片与切片检查的156例（疑似）ET患者标本重新分类,并双盲分析PMF早期与ET患者骨髓形态学差异.收集行JAK2V617F突变检测的22例PMF早期患者与27例ET患者标本,双盲比较JAK2V617F突变型与野生型骨髓形态学差异.结果 156例（疑似）ET患者标本中PMF早期61例（MF-0为34例,MF-1为27例）、PMF明显期12例、ET83例.MF-1组患者血小板计数[（1134 ＋391）×109/L]、血清乳酸脱氢酶水平[（727±241）U/L]显著高于ET组[（973±242）×109/L,（392±146）U/L] （P ＜0.05）.MF-1组患者骨髓涂片中原始细胞比例（0.012±0.010）显著高于ET组（0.006＋0.004）（P＜0.05）.MF-0与MF-1组患者骨髓切片示有核细胞（粒细胞）总量增多、紧密型巨核细胞簇、骨小梁旁巨核细胞、云雾状巨核细胞、小裸核巨核细胞、大单圆核巨核细胞的检出率均显著高于ET组,而疏松型巨核细胞簇、巨大多分叶核巨核细胞的检出率均显著低于ET组（P值均＜0.05）；MF-1组患者巨核细胞簇伴异形性改变的检出率显著高于MF-0与ET组（P值均＜0.05）.PMF早期与ET患者JAK2V617F突变阳性率分别为54.5％与48.1％.PMF早期与ET组突变型患者HGB水平均高于野生型（P值均＜0.05）,而巨核细胞形态在突变型中均未见明显异形性改变.结论 骨髓切片形态学（尤其是巨核细胞形态学）是PMF早期与ET鉴别诊断的基础,形态学参数的重要性排序依次为巨核细胞簇伴异形性、云雾状巨核细胞、大单圆核巨核细胞、有核细胞（粒细胞）总量增多、小裸核巨核细胞、骨小梁旁巨核细胞及紧密型巨核细胞簇.

Objective To compare the morphologic features of bone marrow （BM） between the prefibrotic-early primary myelofibrosis （PMF） and essential thrombocythaemia （ET）. Method Seven cases of prefibrotic-early PMF were selected and analyzed. Based on the diagnostic standard of prefibrotic-early PMF by WHO, BM aspirate smears, trephine biopsy sections and imprints of 156 uncertain ET cases conducted simultaneously were recruited into this study, the BM morphologic features between the prefibrotic-early PMF and ET groups were analyzed. The morphological difference in 22 cases of prefibrotic-early PMF and 27 ET were compared between the JAK2V617F mutation positive and negative groups. Results Of the 156 uncertain ET cases, it was reclassified 61 prefibrotic-early PMF （34 MF-0, 27 MF-1 ）, 12 PMF and 83 ET. The platelet count and LDH level in MF-1 group were obviously higher than that of ET group （ P 〈 0.05 ）. The blast percentage of BM smear in MF-1 group was also higher than that of ET group （ P 〈 0.05 ）. As to BM section, cases with increased nucleated cells （granulocyte）, compact megakaryocytic cluster, megakaryocyte near bone trabecula, cloud-like megakaryocyte, small bare nucleus of megakaryocyte and large ball-like megakaryocyte in MF-0 and MF-1 group were significantly higher than that of ET group （ all P 〈 0.05 ）, cases with megakaryocytic cluster of various size in MF-1 group were significantly higher than that of MF-0 and ET groups（P 〈0.05）. The JAK2V617F mutation rate in prefibrotic-early PMF and ET groups were 54.5% and 48.1% , respectively. Hb level in JAK2V617F mutation positive group was obviously higher than the negative group （P 〈 0. 05 ） , no special change with megakaryocytic morphology was found between the positive and negative groups. Conclusion Morphology of BM section, especially megakaryocytic morphologic characteristics are the main basis in distinguishing prefibrotic-early PMF from ET. The importance of morphologic index were megakaryocytic cluster with various size, cloud-like megakaryocyte, large ball-like megakaryocyte, increased nucleated cells （granulocyte）, small bare nucleus, megakaryocyte near bone trabecula and compact megakaryocytic cluster in order. JAK2V617F mutation provides no specific effect on the megakaryocytic morphology.