Petranovic Duska, Pilcic Gorazd, Valkovic Toni, Sotosek Tokmadzic Vlatka, Laskarin Gordana
Department of Internal Medicine, Hematology, Clinical Hospital Center Rijeka, Faculty of Medicine, University of Rijeka, 51000 Rijeka, B. Branchetta 20, Croatia.
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, B. Branchetta 20, Croatia; Department of Anesthesiology, Reanimatology and Intensive Care, Faculty of Medicine, University of Rijeka, 51000 Rijeka, B. Branchetta 20, Croatia.
Med Hypotheses. 2014 Jul;83(1):122-6. doi: 10.1016/j.mehy.2014.03.024. Epub 2014 Apr 1.
Acute lymphoblastic leukaemia (ALL) is an aggressive disease. The course of disease is regulated by pro-inflammatory agents, and malignant cell infiltration of tissues plays a deleterious role in disease progression, greatly impacting quality of life, especially in the cognitive domains. Our hypothesis is that significant serum concentrations of interleukin 15 (IL-15) are responsible for higher expression of adhesion molecules on endothelial cells of blood-brain barrier (BBB) which allow leukaemia cells and/or normal lymphocytes the infiltration into the brain. In brain tissue these cells could be stimulated to release perforin and granulysin causing induction of apoptosis in brain cells that are involved in complex neural signalling mediated by neurotransmitters, and consequent fine cognitive impairment. Such changes could be detected early, even before notable clinical psycho-neurological or radiological changes in patients with ALL. To evaluate this hypothesis we propose measuring cognitive function using Complex Reactiometer Drenovac (CRD) scores in patients with ALL. The expression of different adhesion molecules on BBB as well as presence and distribution of different lymphocytes in brain tissue will be analyzed. We will then correlate CRD scores with levels of IL-15 and the percentages of T cells, natural killer T cells, and natural killer cells expressing perforin and/or granulysin proteins. CRD is a scientifically recognised and highly sensitive psychometric laboratory test based on the complex chronometric mathematical measuring of speed of reaction to various stimuli. It provides an objective assessment of cognitive functions from the most complex mental activities to the simplest reaction reflexes. Early recognition of cognitive dysfunction might be important when selecting the most appropriate chemotherapy and/or radiotherapy regimens, and could allow for the implementation of preventive measures against further deterioration in cognitive function and quality of life in patients with ALL.
急性淋巴细胞白血病（ALL）是一种侵袭性疾病。疾病进程受促炎因子调节，组织中的恶性细胞浸润在疾病进展中起有害作用，极大地影响生活质量，尤其是在认知领域。我们的假设是，血清中白细胞介素15（IL-15）的显著浓度导致血脑屏障（BBB）内皮细胞上黏附分子的高表达，从而使白血病细胞和/或正常淋巴细胞浸润到大脑中。在脑组织中，这些细胞可能被刺激释放穿孔素和颗粒溶素，导致参与神经递质介导的复杂神经信号传导的脑细胞凋亡，进而导致细微的认知障碍。即使在ALL患者出现明显的临床精神神经或放射学变化之前，这些变化也能被早期检测到。为了评估这一假设，我们建议使用Complex Reactiometer Drenovac（CRD）评分来测量ALL患者的认知功能。将分析BBB上不同黏附分子的表达以及脑组织中不同淋巴细胞的存在和分布。然后，我们将把CRD评分与IL-15水平以及表达穿孔素和/或颗粒溶素蛋白的T细胞、自然杀伤T细胞和自然杀伤细胞的百分比进行关联。CRD是一种科学认可且高度敏感的心理测量实验室测试，基于对各种刺激反应速度的复杂计时数学测量。它能从最复杂的心理活动到最简单的反应反射对认知功能进行客观评估。在选择最合适的化疗和/或放疗方案时，早期识别认知功能障碍可能很重要，并且可以采取预防措施防止ALL患者的认知功能和生活质量进一步恶化。
