-
急性髓系白血病(AML)为骨髓造血细胞恶性增殖疾病,主要表现为造血系统异常,包括白细胞异常、不同程度贫血、凝血功能障碍,还伴有发热和肝脾淋巴结肿大,以造血细胞分化障碍和造血干细胞/祖细胞无限增殖为主要发病机制,如不及时治疗, 可导致病人迅速骨髓衰竭并最终死亡。AML是成人最常见的白血病类型,随着科学研究的不断深入,AML的治疗手段也更加多样化,多种治疗手段相互补充,使AML的治疗水平得到很大提升,但仍然存在不良反应大、微小残留细胞白血病难以根治等难题[1],仍需继续深入探讨AML的发病机制,为AML的诊疗提供新的思路。FBXO22已被证实参与多种肿瘤的发生、发展和信号转导,但是其在AML病人体内的表达情况和临床作用尚未被阐明。本研究探讨AML病人骨髓细胞中FBXO22 mRNA表达情况及其与病人临床指征的相关关系。现作报道。
-
各组FBXO22 mRNA表达水平间差异有统计学意义(P<0.01),其中PR组和初发组均低于对照组和CR组(P<0.05),而对照组和CR组、PR组和初发组间差异均无统计学意义(P>0.05)(见表 1)。
分组 n FBXO22 mRNA F P MS组内 对照组 30 1.07±0.37 39.20 < 0.01 0.087 初发组 41 0.40±0.18* PR组 23 0.50±0.24* CR组 28 0.93±0.37△# q检验:与对照组比较*P<0.05;与初发组比较△P<0.05;与PR组比较#P<0.05 表 1 各组病人FBXO22 mRNA相对表达量比较(x±s)
-
不同性别、年龄、贫血程度、白细胞计数、临床分型的初发组病人FBXO22 mRNA表达水平差异均无统计学意义(P>0.05),而不同血小板计数病人的FBXO22 mRNA表达水平差异有统计学意义(P<0.05)(见表 2)。相关分析显示,初发组病人血小板计数与FBXO22 mRNA相对表达水平呈明显正相关关系(r=0.492,P<0.01)。
指标 n FBXO22 mRNA相对表达量 F P MS组内 性别 男 25 0.45±0.18 1.88* >0.05 — 女 16 0.34±0.17 年龄/岁 ≤48 12 0.45±0.18 1.06* >0.05 — >48 29 0.38±0.18 白细胞计数/(×109/L) < 50 26 0.41±0.20 0.20* >0.05 — ≥50 15 0.40±0.18 贫血 轻度 9 0.35±0.22 0.87 >0.05 0.034 中度 18 0.39±0.19 重度 14 0.45±0.15 血小板计数/(×109/L) < 30 16 0.31±0.18 6.64 < 0.01 0.027 30~100 20 0.43±0.16 >100 5 0.61±0.14 分型/型 M0 2 0.42±0.14 0.57 >0.05 0.035 M1 4 0.44±0.26 M2 13 0.35±0.19 M3 4 0.35±0.14 M4 5 0.49±0.15 M5 13 0.43±0.19 * 示t值 表 2 不同临床指标的初发组病人FBXO22 mRNA相对表达量比较(x±s)
FBXO22在急性髓系白血病中的表达分析
Expression analysis of FBXO22 in acute myeloid leukemia
-
摘要:
目的检测急性髓系白血病(AML)病人骨髓细胞FBXO22基因表达水平,分析其与病人临床指征的相关性。 方法收集AML病人92例,其中初发组41例,完全缓解(CR)组28例,部分缓解(PR)组23例,另选取肾性贫血、缺铁性贫血病人30例作为对照组。实时荧光定量PCR法测定并比较各组病人骨髓细胞中FBXO22 mRNA相对表达量。分析初发组病人FBXO22 mRNA相对表达量与病人性别、年龄、血常规参数、临床分型的相关性。 结果各组病人FBXO22 mRNA表达水平间差异有统计学意义(P<0.01),其中PR组和初发组均低于对照组和CR组(P<0.05),而对照组和CR组、PR组和初发组间差异均无统计学意义(P>0.05)。初发组病人中,不同血小板计数病人的FBXO22 mRNA表达水平差异有统计学意义(P<0.05)。相关分析显示,初发组病人血小板计数与FBXO22 mRNA相对表达水平呈明显正相关关系(r=0.492,P<0.01)。 结论AML病人骨髓细胞FBXO22表达降低,且与血小板计数呈正相关关系。 Abstract:ObjectiveTo detect the expression level of FBXO22 gene in bone marrow cells of patients with acute myeloid leukemia (AML), and analyze its correlation with clinical indications. MethodsA total of 92 AML cases were collected, including 41 cases in the primary group, 28 cases in the complete remission (CR) group, 23 cases in the partial remission (PR) group, and 30 cases with renal anemia and iron deficiency anemia in the control group.The relative expression of FBXO22 mRNA in bone marrow cells was detected by real-time fluorescence quantitative PCR.The correlation between the expression of FBXO22 mRNA and the patient's gender, age, blood routine parameters and clinical classification of patients were analyzed in the primary group. ResultsThere was a statistically significant difference in the expression level of FBXO22 mRNA among patients in each group (P<0.01).The levels of FBXO22 mRNA in the PR group and primary group were lower than those in the control group and CR group (P<0.05), but there was no statistically significant difference between the control group and CR group, PR group and primary group (P>0.05).There was significant difference in the expression level of FBXO22 mRNA among patients with different platelet counts in the primary group (P<0.05).Correlation analysis showed that there was a significant positive correlation between the platelet count and the relative expression level of FBXO22 mRNA in the primary group (r=0.492, P<0.01). ConclusionsThe expression of FBXO22 in bone marrow of patients with AML is decreased, and positively associates with platelet count. -
Key words:
- acute myeloid leukemia /
- FBXO22 /
- platelet count
-
表 1 各组病人FBXO22 mRNA相对表达量比较(x±s)
分组 n FBXO22 mRNA F P MS组内 对照组 30 1.07±0.37 39.20 < 0.01 0.087 初发组 41 0.40±0.18* PR组 23 0.50±0.24* CR组 28 0.93±0.37△# q检验:与对照组比较*P<0.05;与初发组比较△P<0.05;与PR组比较#P<0.05 表 2 不同临床指标的初发组病人FBXO22 mRNA相对表达量比较(x±s)
指标 n FBXO22 mRNA相对表达量 F P MS组内 性别 男 25 0.45±0.18 1.88* >0.05 — 女 16 0.34±0.17 年龄/岁 ≤48 12 0.45±0.18 1.06* >0.05 — >48 29 0.38±0.18 白细胞计数/(×109/L) < 50 26 0.41±0.20 0.20* >0.05 — ≥50 15 0.40±0.18 贫血 轻度 9 0.35±0.22 0.87 >0.05 0.034 中度 18 0.39±0.19 重度 14 0.45±0.15 血小板计数/(×109/L) < 30 16 0.31±0.18 6.64 < 0.01 0.027 30~100 20 0.43±0.16 >100 5 0.61±0.14 分型/型 M0 2 0.42±0.14 0.57 >0.05 0.035 M1 4 0.44±0.26 M2 13 0.35±0.19 M3 4 0.35±0.14 M4 5 0.49±0.15 M5 13 0.43±0.19 * 示t值 -
[1] 孔令环, 韩梅, 马寅芙, 等. 急性髓系白血病微小残留病检测的临床意义[J]. 中国实验诊断学, 2011, 15(4): 636. [2] 沈悌, 赵永强. 血液病诊断及疗效标准[M]. 4版. 北京: 科学出版社, 2018: 87. [3] 林冬, 魏辉, 王迎, 等. FLT3-ITD突变阳性急性髓系白血病的临床特征和预后因素[J]. 中华血液学杂志, 2016, 37(12): 1017. [4] HUANG XD, VISHVA M. Crosstalk between autophagy and proteasome protein degradation systems possible implications for cancer therapy[J]. Folia Histochem Cytobiol, 2013, 51(4): 249. [5] LIU WJ, YE L, HUANG WF, et al. p62 links the autophagy pathway and the ubiquitinproteasome system upon ubiquitinated protein degradation[J]. Cell Mol Biol Lett, 2016, 21: 29. doi: 10.1186/s11658-016-0031-z [6] EBNER PA, VERSTEEG G, IKEDA F. Ubiquitin enzymes in the regulation of immune responses[J]. Crit Rev Biochem Mol Biol, 2017, 52(4): 425. doi: 10.1080/10409238.2017.1325829 [7] TIAN X, DAI SD, SUN J, et al. F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression[J]. Oncotarget, 2015, 6(26): 22767. doi: 10.18632/oncotarget.4082 [8] ZHANG L, CHEN J, NING D, et al. FBXO22 promotes the development of hepatocellular carcinoma by regulating the ubiquitination and degradation of p21[J]. J Exp Clin Cancer Res, 2019, 38(1): 101. doi: 10.1186/s13046-019-1058-6 [9] ZHU XN, HE P, ZHANG L, et al. FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth[J]. Cell Death Dis, 2019, 10(7): 486. doi: 10.1038/s41419-019-1732-9 [10] HOU XK, MAO JS. Long noncoding RNA SNHG14 promotes osteosarcoma progression via miR-433-3p/FBXO22 axis[J]. Biochem Biophys Res Commun, 2020, 523(3): 766. doi: 10.1016/j.bbrc.2020.01.016 [11] 宋虎, 张亚飞, 徐为, 等. FBXO22对结肠癌细胞侵袭迁移的影响及相关机制[J]. 南京医科大学学报(自然科学版), 2017, 37(12): 1553. doi: 10.7655/NYDXBNS20171203 [12] 胡林义, 张萌, 白津, 等. FBXO22在卵巢癌中的表达和临床意义[J]. 徐州医科大学报, 2018, 38(3): 191. [13] HE YR, WANG YF, LIU L, et al. Circular RNA circ_0006282 contributes to the progression of gastric cancer by sponging miR-155 to upregulate the expression of FBXO22[J]. Onco Targets Ther, 2020, 13: 1001. doi: 10.2147/OTT.S228216 [14] GUO F, LIU JJ, HAN X, et al. FBXO22 suppresses metastasis in human renal cell carcinoma via inhibiting MMP-9-mediated migration and invasion and VEGF-mediated angiogenesis[J]. Int J Biol Sci, 2019, 15(3): 647. doi: 10.7150/ijbs.31293 [15] 方虹舒, 张薇. FBXO22对乳腺癌细胞侵袭迁移能力的影响[J]. 国际检验医学杂志, 2019, 40(10): 1157. doi: 10.3969/j.issn.1673-4130.2019.10.002 [16] SUN R, XIE HY, QIAN JX, et al. FBXO22 possesses both protumorigenic and antimetastatic roles in breast cancer progression[J]. Cancer Res, 2018, 78(18): 5274. doi: 10.1158/0008-5472.CAN-17-3647 [17] JOHMURA Y, SUN J, KITAGAWA K, et al. SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence[J]. Nat Commun, 2016, 7: 10574. doi: 10.1038/ncomms10574 [18] ZHENG XQ, YU SW, XUE Y, et al. FBXO22, ubiquitination degradation of PHLPP1, ameliorates rotenone induced neurotoxicity by activating AKT pathway[J]. Toxicol Lett, 2021, 350: 1. doi: 10.1016/j.toxlet.2021.06.017 [19] SUZUKI N, JOHMURA Y, WANG T, et al. TP53/p53-FBXO22-TFEB controls basal autophagy to govern hormesis[J]. Autophagy, 2021, 17(11): 1. [20] WU B, LIU ZY, CUI J, et al. F-Box protein FBXO22 mediates polyubiquitination and degradation of CD147 to reverse cisplatin resistance of tumor cells[J]. Int J Mol Sci, 2017, 18(1): 212. [21] DIKOPOLTSEV E, FOLTYN V, ZEHL M, et al. FBXO22 protein is required for optimal synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine[J]. J Biol Chem, 2014, 289(49): 33904. [22] 姜艳红, 焦扬, 陈光意, 等. 不同血小板数量分层在儿童初治原发急性髓系白血病中的临床意义[J]. 中华实用儿科临床杂志, 2021, 36(3): 204. [23] 庞艳彬, 范丽霞, 赵松颖, 等. 首次诱导治疗后的血小板计数与急性髓系白血病无复发生存期的关系[J]. 广东医学, 2018, 39(5): 717. [24] 向丹, 沈建良, 黄有章, 等. 巨核细胞、血小板动态变化对急性白血病疗效和预后的意义150例分析与文献复习[J]. 海军总医院学报, 2004, 12(7): 109.