Al-Kawaaz Mustafa, Sanchez Teresa, Kluk Michael J
Weill Cornell Medicine, Dept. of Pathology and Laboratory Medicine New York, NY, USA.
Weill Cornell Medicine, Dept. of Neuroscience, Brain and Mind Research Institute, New York, NY, USA.
J Hematop. 2019 Jun;12(2):57-65. doi: 10.1007/s12308-019-00354-y. Epub 2019 Apr 27.
Aggressive, mature B-cell lymphomas include Burkitt Lymphoma (BL), High Grade B Cell Lymphomas (HGBL) (eg, Double-Hit B cell lymphomas (HGBL-DH: HGBL with MYC and BCL2 and/or BCL6 translocations)), HGBL, Not Otherwise Specified (HGBL, NOS) and Diffuse Large B Cell Lymphoma (DLBCL). Overlapping morphologic and immunohistochemical features of these lymphomas pose diagnostic challenges in some cases, and better understanding of potential diagnostic biomarkers and possible therapeutic targets is needed. Sphingosine 1 Phosphate Receptors (S1PR1-5) are G-protein coupled receptors that bind S1P and influence migration and survival in multiple cell types, including lymphocytes. S1PRs are emerging as biomarkers in B cell biology and interaction between S1PR pathways and STAT3 or FOXP1 has been reported in DLBCL.
Our aim was to extend the understanding of S1PR1, STAT3 and S1PR2, FOXP1 expression beyond DLBCL, into additional aggressive, mature B cell lymphomas using immunohistochemical expression analysis of human tissue samples.
S1PR1 and S1PR2 showed different expression patterns in mantle zones and follicle centers in reactive lymphoid tissue. BL showed a unique expression pattern compared to HGBL and DLBCL. Additionally, S1PR1 and S1PR2 expression were typically mutually exclusive and were expressed in a low proportion of cases (frequently HGBL involving extranodal sites). FOXP1 was expressed in a high proportion of various case types and pSTAT3 was detected in a significant proportion of HGBL and DLBCL.
These findings provide further evidence that S1PR1, pSTAT3, S1PR2 and FOXP1 play a role in a subset of aggressive, mature B cell lymphomas.
侵袭性成熟B细胞淋巴瘤包括伯基特淋巴瘤(BL)、高级别B细胞淋巴瘤(HGBL)(例如,双打击B细胞淋巴瘤(HGBL-DH:伴有MYC和BCL2及/或BCL6易位的HGBL))、未另行指定的HGBL(HGBL,NOS)和弥漫性大B细胞淋巴瘤(DLBCL)。这些淋巴瘤重叠的形态学和免疫组化特征在某些情况下给诊断带来挑战,因此需要更好地了解潜在的诊断生物标志物和可能的治疗靶点。1-磷酸鞘氨醇受体(S1PR1-5)是G蛋白偶联受体,可结合1-磷酸鞘氨醇(S1P)并影响多种细胞类型(包括淋巴细胞)的迁移和存活。S1PR在B细胞生物学中逐渐成为生物标志物,并且在DLBCL中已报道S1PR途径与STAT3或FOXP1之间存在相互作用。
我们的目的是通过对人体组织样本进行免疫组化表达分析,将对S1PR1、STAT3以及S1PR2、FOXP1表达的理解从DLBCL扩展到其他侵袭性成熟B细胞淋巴瘤。
S1PR1和S1PR2在反应性淋巴组织的套区和滤泡中心显示出不同的表达模式。与HGBL和DLBCL相比,BL表现出独特的表达模式。此外,S1PR1和S1PR2的表达通常相互排斥,且在低比例病例中表达(常见于累及结外部位的HGBL)。FOXP1在多种病例类型中高比例表达,而磷酸化STAT3(pSTAT3)在相当比例的HGBL和DLBCL中被检测到。
这些发现进一步证明S1PR1、pSTAT3、S1PR2和FOXP1在一部分侵袭性成熟B细胞淋巴瘤中发挥作用。