Background

The High Mobility Group Box 1 (HMGB1) is a nuclear protein that is frequently overexpressed in hematologic diseases and might be of relevance in immunogenic cancer control thus correlating with patients’ (pts.) prognosis in diseases such as acute myeloid, acute lymphatic and chronic lymphocytic leukemia.

Materials and methods

Expression profiles of blasts from AML (n = 21), ALL (n = 16) and of B-lymphocytes of CLL (n = 9) pts. were analyzed for surface expression of HMGB1 using flow cytometry. Expression was quantified and correlated with clinically and prognostically relevant markers.

Results

Expression profiling of HMGB1 in blasts of AML and ALL subtypes did not show differences between primary vs. secondary disease development and gender related differences. In ALL pts. however, age groups at initial diagnosis between ≥20 vs. <20 years were compared and showed significant differences (≥20 vs. <20 years; 89% vs. 49%, p <0.05) with higher expression in higher age. In AML and CLL these differences were not visible. To evaluate the prognostic significance of HMGB1 expression, expression quantity was correlated with established and prognostic classification systems (in AML ELN, in ALL GMALL) and probability to relapse. No significant correlation was seen in these entities. However, when AML pts. were analyzed for remission rates after first anthracycline based induction therapy, in those who did not experience a complete remission significantly enhanced HMGB1 surface expression was seen (98 vs. 94%; p < 0.05; n = 20). Furthermore, for CLL it was shown that higher HMGB1 expression was found in pretreated patients with relapsed or/and refractory disease (1 vs. more relapses; 94 vs. 98%; p <0.05; n = 9).

Conclusion

HMGB1 is frequently expressed in hematologic malignancies. In this study it was shown that HMGB1 surface expression on AML blasts can be used as predictors for treatment response. In CLL it may be a marker for advanced disease. In order to implement this marker in FACS routine it could be a useful and practical tool for prognostic assessment and treatment planning.

中文翻译：

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B-CLL相关白细胞上HMGB1的表达谱有助于预测复发

背景

High Mobility Group Box 1 (HMGB1) 是一种核蛋白，在血液系统疾病中经常过度表达，可能与免疫原性癌症控制相关，因此与患者 (pts.) 在急性髓细胞、急性淋巴和慢性疾病等疾病中的预后相关淋巴细胞白血病。

材料和方法

来自 AML (n = 21)、ALL (n = 16) 和 CLL (n = 9) pts 的 B 淋巴细胞的原始细胞的表达谱。使用流式细胞术分析HMGB1的表面表达。表达被量化并与临床和预后相关的标志物相关联。

结果

HMGB1 在 AML 和 ALL 亚型的原始细胞中的表达谱未显示原发性与继发性疾病发展和性别相关差异之间的差异。在所有积分中。然而，对≥20 岁与 <20 岁之间的初始诊断年龄组进行比较，结果显示出显着差异（≥20 岁与 <20 岁；89% 与 49%，p <0.05），年龄越大表达越高。在 AML 和 CLL 中，这些差异不可见。为了评估 HMGB1 表达的预后意义，表达量与已建立的预后分类系统（在 AML ELN、ALL GMALL 中）和复发概率相关。在这些实体中未发现显着相关性。然而，当 AML 分。分析第一次基于蒽环类药物的诱导治疗后的缓解率，在那些没有经历完全缓解的人中，HMGB1 表面表达显着增强（98 对 94%；p < 0.05；n = 20）。此外，对于 CLL，显示在接受过治疗的复发或/和难治性疾病患者中发现更高的 HMGB1 表达（1 对更多复发；94 对 98%；p <0.05；n = 9）。

结论

HMGB1 经常在血液系统恶性肿瘤中表达。在这项研究中，表明 AML 原始细胞上的 HMGB1 表面表达可用作治疗反应的预测因子。在 CLL 中，它可能是晚期疾病的标志物。为了在 FACS 常规中实施该标记，它可能是预后评估和治疗计划的有用且实用的工具。