[1]纪婷婷,陶善东,丁邦和,等.非M3型急性髓系白血病患者骨髓原始细胞酪氨酸蛋白激酶CD117的表达及意义[J].新乡医学院学报,2024,(4):353-357.[doi:10.7683/xxyxyxb.2024.04.010]
 JI Tingting,TAO Shandong,DING Banghe,et al.Expression of tyrosine protein kinase CD117 in patients with non-M3 acute myeloid leukemia and its significance[J].Journal of Xinxiang Medical University,2024,(4):353-357.[doi:10.7683/xxyxyxb.2024.04.010]
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非M3型急性髓系白血病患者骨髓原始细胞酪氨酸蛋白激酶CD117的表达及意义
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
期数:
2024年4
页码:
353-357
栏目:
临床研究
出版日期:
2024-04-05

文章信息/Info

Title:
Expression of tyrosine protein kinase CD117 in patients with non-M3 acute myeloid leukemia and its significance
作者:
纪婷婷12陶善东12丁邦和12王春玲12于亮12
(1.南京医科大学附属淮安第一医院血液科,江苏 淮安 223300;2.南京医科大学血液病重点实验室,江苏 南京 210009)
Author(s):
JI Tingting12TAO Shandong12DING Banghe12WANG Chunling12YU Liang12
(1.Department of Hematology,the Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University,Huai′an 223300,Jiangsu Province,China;2.Key Laboratory of Hematology,Nanjing Medical University,Nanjing 210009,Jiangsu Province,China)
关键词:
急性髓系白血病免疫表型CD117预后
Keywords:
acute myeloid leukemiaimmunophenotypeCD117prognosis
分类号:
R733.71
DOI:
10.7683/xxyxyxb.2024.04.010
文献标志码:
A
摘要:
目的 探讨酪氨酸蛋白激酶CD117在非M3型急性髓系白血病(AML)患者的表达及其与AML患者疗效和预后的关系。
方法 选择2013年1月至2018年6月淮安市第一人民医院收治的83例初诊为非M3型AML患者为研究对象,根据骨髓原始细胞免疫表型流式细胞术检测结果将患者分为CD117抗原阴性组(CD117-组,n=40)和CD117抗原阳性组(CD117+组,n=43),采用R显带技术分析AML患者的染色体核型,多重反转录聚合酶链式反应法检测AML患者的基因突变情况,结合患者染色体及基因突变结果,将所有患者预后分层为预后良好、预后中等、预后不良。所有患者根据病情选择以下诱导方案中的1种进行化学治疗:(1)IA方案[去甲氧柔红霉素10~12 mg·m-2(第1~3天) +阿糖胞苷100 mg·m-2(第1~7天)];(2)DA方案[柔红霉素60~90 mg·m-2(第1~3天) +阿糖胞苷100 mg·m-2(第1~7天)];(3)HA方案[高三尖杉酯碱2.5 mg·m-2(第1~7天) +阿糖胞苷100 mg·m-2(第1~7天)]。1个疗程后未达完全缓解(CR)的患者可选择原方案或更改诱导方案;达CR的患者选择中大剂量阿糖胞苷(1~2 g·m-2 ,12 h 1次,第1~4天)方案进行巩固化学治疗。患者均完成1个疗程及以上标准诱导化学治疗方案。观察所有患者的CR率、微小残留病(MRD)阴性率及总生存期(OS)。
结果 2组患者的染色体核型及FLT3、CEBPA、NPM1、C-kit等基因突变状态、预后分层比较差异无统计学意义(P>0.05)。CD117-组1个疗程后CR率为77.50%(31/40),CD117+组1个疗程后CR率为76.74%(33/43);2组患者1个疗程后CR率比较差异无统计学意义(χ2=0.007,P>0.05)。CD117-组达CR患者的MRD阴性率为90.30%(28/31),CD117+组达CR患者的MRD阴性率为57.60%(19/33);CD117-组达CR患者的MRD阴性率显著高于CD117+组(χ2=8.797,P<0.01)。CD117-组患者的中位OS为33.09[95%置信区间(CI):28.22~37.97]个月,CD117+组患者的中位OS为20.61(95%CI:17.89~23.33)个月;CD117-组患者的中位OS显著长于CD117+组(P<0.01)。
结论 CD117与非M3型AML患者的MRD相关,是影响AML患者预后的因素,对指导AML患者的临床治疗具有重要意义。
Abstract:
Objective To investigate the expression of tyrosine protein kinase CD117 in non-M3 acute myeloid leukemia (AML) patients and its relationship with the outcome and prognosis of AML patients.
Methods A total of 83 newly diagnosed non-M3 AML patients admitted to the Huai′an First People′s Hospital from January 2013 to June 2018 were selected as the research subjects,and they were divided into the CD117 antigenic negative group (CD117- group,n=40) and CD117 antigenic positive group (CD117+ group,n=43) according to the immunophenotype flow cytometry detection of bone marrow original cells.The chromosome karyotype of AML patients was analyzed using the R-banding technique,and the gene mutation of AML patients was detected by multiplex reverse transcriptase polymerase chain reaction.Based on the results of chromosome karyotype and gene mutation,the prognosis of all patients was stratified into the good prognosis,the medium prognosis,and the poor prognosis.All patients were treated with one of the following induction regimens according to their condition:(1) IA regimen [idarubicin 10-12 mg·m-2 (day 1-3) + cytarabine 100 mg·m-2 (day 1-7)];(2) DA regimen [daunorubicin 60-90 mg·m-2 (day 1-3) + cytarabine 100 mg·m-2 (day 1-7)];(3) HA regimen [homoharringtonine 2.5 mg·m-2 (day 1-7) + cytarabine 100 mg·m-2 (day 1-7)].Patients who did not reach complete remission (CR) after the first course of induction could choose the original regimen or a new regimen.All patients with CR were treated with high-dose cytarabine (1-2 g·m-2,once in 12 hours,day 1-4) for consolidation chemotherapy.All patients completed one course or more of standard induction chemotherapy.The CR rate,minimal residual disease (MRD) negative rate and the overall survival (OS) of all patients were observed.
Results There was no significant difference in chromosome karyotype,FMS-like tyrosine kinase 3 (FLT3),CCAAT/enhancer binding protein α (CEBPA),nucleophosmin 1 (NPM1) and C-kit gene mutations,and stratified prognosis between the two groups (P>0.05).The CR rates after the first treatment course in the CD117- and CD117+ groups were 77.50% (31/40) and 76.74% (33/43),respectively,showing no statistically significant difference between the two groups (χ2=0.007,P>0.05).The MRD negative rate of CR patients in the CD117- group was 90.30% (28/31),and the MRD negative rate in the CD117+ group was 57.60% (19/33).The MRD negative rate of CR patients in the CD117- group was significantly higher than that in the CD117+ group (χ2=8.797,P<0.01).The median OS was 33.09 [95% confidence interval (CI):28.22-37.97] months in the CD117- group and 20.61 (95%CI:17.89-23.33) months in the CD117+ group.The median OS in the CD117- group was significantly longer than that in the CD117+ group (P<0.01).
Conclusion CD117 is associated with the MRD in non-M3 AML patients and affects the prognosis of AML patients.It is of great significance to guide the clinical treatment of AML patients.

参考文献/References:

[1] KAYSER S,LEVIS M J.The clinical impact of the molecular landscape of acute myeloid leukemia[J].〖KG-\*4〗Haematologica,2023,108(2):308-320.
[2] NABIL R,HASSAN N M,ABDELLATEIF M S,et al.The prognostic role of C-KIT,TET1 and TET2 gene expression in acute myeloid leukemia[J].Mol Biol Rep,2023,50(1):641-653.
[3] DHNER H,WEI A H,APPELBAUM F R,et al.Diagnosis and management of AML in adults:2022 recommendations from an international expert panel on behalf of the ELN[J].Blood,2022,140(12):1345-1377.
[4] SIMONS A,SHAFFER L G,HASTINGS R J.Cytogenetic nomenclature:changes in the ISCN 2013 compared to the 2009 edition[J].Cytogenet Genome Res,2013,141(1):1-6.
[5] 中华医学会血液学分会白血病淋巴瘤学组.成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2023年版)[J].中华血液学杂志,2023,44(9):705-712.
LEUKEMIA & LYMPHOMA GROUP,CHINESE SOCIETY OF HEMATOLOGY,CHINESE MEDICAL ASSOCIATION.Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (not APL) (2023)[J].Chin J Hematol,2023,44(9):705-712.
[6] FAN H,LI Y,LIU C,et al.Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203[J].Biochem Biophys Res Commun,2018,507(1/2/3/4):178-184.
[7] 徐涛,颜慕霞,徐令,等.环状RNA circOMA1对儿童急性髓系白血病细胞增殖和凋亡的影响[J].中华实用儿科临床杂志,2022,37(11):831-836.
XU T,YAN M X,XU L,et al.Effects of circular RNA circOMA1 on cell proliferation and apoptosis of children with acute myeloid leukemia[J].Chin J Appl Clin Pediatr,2022,37(11):831-836.
[8] 张晓冬,林晓媛.急性髓系白血病患者外周血调节性T细胞、辅助性T细胞17及其相关细胞因子的表达及意义[J].新乡医学院学报,2023,40(4):339-342,352.
ZHANG X D,LIN X Y.Expression and significance of regulatory T cells,helper T cell 17 cells and their related cytokines in peripheral blood of patients with acute myeloid leukemia[J].J Xinxiang Med Univ,2023,40(4):339-342,352.
〖HJ1.8mm〗[9] STUBBINS R J,FRANCIS A,KUCHENBAUER F,et al.Management of acute myeloid leukemia:a review for general practitioners in oncology[J].Curr Oncol,2022,29(9):6245-6259.
[10] OCHS M A,MARINI B L,PERISSINOTTI A J,et al.Oncology stewardship in acute myeloid leukemia[J].Ann Hematol,2022,101(8):1627-1644.
[11] THIEBLEMONT C,PHILLIPS T,GHESQUIERES H,et al.Epcoritamab,a novel,subcutaneous CD3xCD20 bispecific T-cell-engaging antibody,in relapsed or refractory large B-cell lymphoma:dose expansion in a phase I/II trial[J].J Clin Oncol,2023,41(12):2238-2247.
[12] ZHANG J,HU Y,YANG J,et al.Non-viral,specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL[J].Nature,2022,609(7926):369-374.
[13] SHIMONY S,STAHL M,STONE R M.Acute myeloid leukemia:2023 update on diagnosis,risk-stratification,and management[J].Am J Hematol,2023,98(3):502-526.
[14] KATAGIRI S,CHI S,MINAMI Y,et al.Mutated KIT tyrosine kinase as a novel molecular target in acute myeloid leukemia[J].Int J Mol Sci,2022,23(9):4694.
[15] MATSUNAGA T,TAKEMOTO N,SATO T,et al.Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia[J].Nat Med,2003,9(9):1158-1165.
[16] DINARDO C D,ERBA H P,FREEMAN S D,et al.Acute myeloid leukaemia[J].Lancet,2023,401(10393):2073-2086.
[17] AKRAM A M,HASSAN M,CHAUDHARY A,et al.Identification and in silico analysis of noval alteration Arg420Gly in KIT proto oncogene among acute myeloid leukemia patients[J].Sci Rep,2022,12(1):19252.
[18] SPAARGAREN M.Ibrutinib for AML? Check CD117 (KIT)![J].Lancet Haematol,2015,2(5):e180-e181.
[19] OELLERICH T,MOHR S,CORSO J,et al.FLT3-ITD and TLR9 use Bruton tyrosine kinase to activate distinct transcriptional programs mediating AML cell survival and proliferation[J].Blood,2015,125(12):1936-1947.
[20] RUSHWORTH S A,PILLINGER G,ABDUL-AZIZ A,et al.Activity of Bruton′s tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia:a mechanistic study using patient-derived blast cells[J].Lancet Haematol,2015,2(5):e204-e211.
[21] HEO S K,NOH E K,KIM J Y,et al.Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells[J].Eur J Pharmacol,2017,804:52-56.
[22] HEO S K,NOH E K,KIM J Y,et al.Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death[J].Sci Rep,2017,7(1):15278.
[23] 陶善东,邓媛,何正梅,等.Btk及NFκB在急性髓系白血病细胞中的表达及其意义[J].中国实验血液学杂志,2013,21(1):25-28.
TAO S D,DENG Y,HE Z M,et al.Expression of Btk and NFκB in acute myeloid leukemia cells and its significance[J].J Exp Hematol,2013,21(1):25-28.

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更新日期/Last Update: 2024-04-05