Zare-Abdollahi D, Safari S, Movafagh A, Ghadiani M, Tabarraee M, Riazi-Isfahani S, Gorji S, Keyvan L, Gachkar L
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Hemato-Oncology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Int J Lab Hematol. 2016 Apr;38(2):125-32. doi: 10.1111/ijlh.12454. Epub 2016 Jan 13.
In acute myeloid leukemia (AML), it has been shown that AML-derived cells often remain sensitive to autophagy-inducing stimuli, leading to the idea that harnessing the autophagy can be pertinent to AML cytotoxic therapy. Despite this promising notion, to date, there is no comprehensive study addressing autophagy-related genes expression status in AML. As a critical mediator, BECN1 influences the onset and advance of autophagy and several studies have pointed to the BECN1 recurrent allelic deletion and expression variation in a broad range of tumors. To explore this caveat, we chose this alteration-prone gene to investigate in our study.
We have analyzed the expression status of BECN1 in a series of 128 de novo AML patients using real-time quantitative polymerase chain reaction (qRT-PCR).
In our favorable subgroup, BECN1 expression did not alter (P = 0.301), but in intermediate and unfavorable patients, we have had BECN1 low expression compared to the normal controls (P = 0.008 and P < 0.001, respectively). We found evidence for the association of reduced expression of BECN1 with FLT3-ITD mutation (19 of 27 patients), monosomal karyotype (all of 11 patients), higher age, and WBC count.
Overall, remarkable association of reduced expression of BECN1 with FLT3-ITD mutation and monosomal karyotype and their functional relationship is interesting which should be addressed and verified in future studies.
在急性髓系白血病（AML）中，研究表明AML来源的细胞通常对自噬诱导刺激保持敏感，这引发了利用自噬进行AML细胞毒性治疗的想法。尽管有这个有前景的概念，但迄今为止，尚无全面研究探讨AML中自噬相关基因的表达状态。作为关键介质，BECN1影响自噬的发生和进展，多项研究指出BECN1在多种肿瘤中存在反复的等位基因缺失和表达变异。为探究这一问题，我们在研究中选择了这个易于发生改变的基因进行研究。
我们使用实时定量聚合酶链反应（qRT-PCR）分析了128例初发AML患者中BECN1的表达状态。
在我们的良好亚组中，BECN1表达未改变（P = 0.301），但在中危和高危患者中，与正常对照相比，我们发现BECN1表达较低（分别为P = 0.008和P < 0.001）。我们发现BECN1表达降低与FLT3-ITD突变（27例患者中的19例）、单倍体核型（11例患者全部）、较高年龄和白细胞计数相关的证据。
总体而言，BECN1表达降低与FLT3-ITD突变和单倍体核型的显著关联及其功能关系很有趣，应在未来研究中加以探讨和验证。
