Gibson Sarah E, Schade Andrew E, Szpurka Hadrian, Bak Beata, Maciejewski Jaroslaw P, Hsi Eric D
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Hum Pathol. 2008 Jul;39(7):1111-4. doi: 10.1016/j.humpath.2007.10.034. Epub 2008 May 13.
Abnormal nuclear megakaryocytic staining for phospho-STAT5 (pSTAT5) correlates with JAK2 V617F mutational status in non-chronic myelogenous leukemia chronic myeloproliferative disorders. However, a proportion of wild-type JAK2 non-chronic myelogenous leukemia chronic myeloproliferative disorders cases also demonstrate this abnormal pSTAT5 expression pattern. We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation. The patient was a 71-year-old man with anemia and thrombocythemia on laboratory examination. His peripheral blood smear demonstrated occasional dysplastic neutrophils. Bone marrow biopsy revealed hypercellular marrow with features consistent with myeloproliferative/myelodysplastic syndrome. Immunohistochemistry for pSTAT5 showed abnormal nuclear megakaryocyte positivity. Cytogenetic analysis revealed a normal karyotype, fluorescence in situ hybridization for BCR-ABL was negative, and JAK2 genotyping demonstrated wild-type JAK2. However, MPL genotyping showed a MPL W515L mutation. Abnormal nuclear megakaryocytic staining for pSTAT5 expression, previously associated with the JAK2 V617F mutation, is also associated with MPL W515L, likely reflecting activation of the JAK-STAT signaling pathway.
在非慢性粒细胞白血病慢性骨髓增殖性疾病中，磷酸化信号转导及转录激活因子5（pSTAT5）的核巨核细胞染色异常与JAK2 V617F突变状态相关。然而，一部分野生型JAK2非慢性粒细胞白血病慢性骨髓增殖性疾病病例也表现出这种异常的pSTAT5表达模式。我们报告了1例JAK2 V617F阴性的骨髓增殖性/骨髓增生异常综合征患者，其巨核细胞pSTAT5表达异常且存在MPL W515L突变。该患者为71岁男性，实验室检查显示贫血和血小板增多。其外周血涂片可见偶发的发育异常的中性粒细胞。骨髓活检显示骨髓细胞增多，具有与骨髓增殖性/骨髓增生异常综合征相符的特征。pSTAT5免疫组化显示核巨核细胞异常阳性。细胞遗传学分析显示核型正常，BCR-ABL荧光原位杂交阴性，JAK2基因分型显示为野生型JAK2。然而，MPL基因分型显示存在MPL W515L突变。先前与JAK2 V617F突变相关的pSTAT5表达的核巨核细胞染色异常，也与MPL W515L相关，这可能反映了JAK-STAT信号通路的激活。
