Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study
Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study
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DOI：
10.1002/ajh.24376
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发表时间：
2016-07-01
影响因子：
12.8
通讯作者：
Wilcox, Ryan A.
中科院分区：
文献类型：
--
作者：
Friedman, Daphne R.;Sibley, Alexander B.;Wilcox, Ryan A.
单核细胞来源的细胞是癌症微环境的组成部分，通过直接的细胞间相互作用和分泌因子在体外支持慢性淋巴细胞白血病（CLL）细胞的存活。我们假设循环绝对单核细胞计数（AMC）反映了微环境中单核细胞来源的细胞，较高的AMC与体内CLL细胞存活率增加相关，因此CLL患者的预后较差。我们评估了诊断CLL时AMC与临床结果的相关程度，以及该信息是否增加了当前使用的预后标志物。我们评估了在梅奥诊所、杜克大学医学中心和达勒姆退伍军人医疗中心随访的1168名CLL患者的AMC、临床使用的预后标志物和事件发生时间数据。AMC升高与较差的临床结果显著相关，包括首次治疗时间（TTT）和总生存期（OS）。AMC联合已建立的临床和分子预后标志物可显著改善慢性淋巴细胞白血病患者TTT的风险分层。由于诊断时AMC升高与疾病进展加速相关，并且CLL微环境中的单核细胞源性细胞促进CLL细胞的存活和增殖，这些发现表明单核细胞和单核细胞源性细胞是CLL合理的治疗靶点。(C) 2016 Wiley期刊公司
Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk-stratification of CLL patients for TTT. As an elevated AMC at diagnosis is associated with accelerated disease progression, and monocyte-derived cells in the CLL microenvironment promote CLL cell survival and proliferation, these findings suggest that monocytes and monocyte-derived cells are rational therapeutic targets in CLL. (C) 2016 Wiley Periodicals, Inc.