伴异柠檬酸脱氢酶1基因突变急性髓系白血病的临床特征及预后

doi:10.19739/j.cnki.issn1001-9510.2021.02.006

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (1236 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To assess the frequencies and clinical characteristics and prognostic significance of the isocitrate dehydrogenase 1(IDH1)mutations in acute myeloid leukemia (AML).Methods Two hundred and twenty patients with AML newly diagnosed in our hospital from January 2015 to September 2018 were selected. PCR was used to amplify the exon 4 of IDH1 gene, gene sequencing was used to detect the mutation of IDHL gene, and the clinical characteristics and prognostic significance of patients with IDH1 mutation were analyzed.Results IDH1 gene mutation was detected in 9 of 220 AML patients, and the mutation rate was 4.09%, all of which were R132H mutation. The median age was 50 years in the mutation group and 43 years old in the non-mutation group, and there was a difference between the two groups, P＜0.05. Blood platelets median level was 68×10⁹/L in the mutated group and 43×10⁹/L in the non-mutation group, and there was a difference between the two groups, P＜0.05. IDH1 gene mutations all occurred in AML-M4/M5, and they were not observed in other AML subtypes. The rate of IDH1mutations was 6.48% in AML with normal karyotype, higher than 1.43%in AML with abnormal karyotype, without signifi cant differences. IDH1 gene mutations were associated with NPM1mutations, P＜0.05, but not associated with FLT3-ITD muta -tions. Patients with IDH1 mutations were prone to CD34^-、CD33⁺、CD64⁺ (averge P<0.05). IDH1 mutated patients hada lower complete remission rate than unmutated patients (50% vs 80.92%), P＜0.05. In all follow-up patients, the 2-year over all survival rate in IDH1 mutation group was lower than in the non-mutation group (25% vs 67.32%), P＜0.05. In the patients with normal karyotype, the 2 years overall survival rate in the IDH1 mutation group was lower than in the non-mutation group (28.57% vs 65.91%), P＜0.05. In the patients without mutated NPM1, the same result was obtain (0% vs 67.20%), P＜0.05. In the patients with mutated NPM1, the 2 years overall survival rate was 40% in the IDH1 mutation group and 67.86% in the non-mutation group, without statistical differences.Conclusion IDH1 gene mutations are more common in AML patients with older age, higher platelets level. IDH1 gene mutations are associated with normal karyotype, AML-M5/M4 and NPMl gene mutations. IDH1 gene mutation was correlated with NPM1 gene mutation. IDH1 gene mutation has an adverse effect on the prognosis of AML patients and is a molecular marker of poor prognosis. In the patients with mutated NPM1, IDH1 gene mutations have no effect on prognosis.

Key words： acute myeloid leukemia isocitrate dehydrogenase gene 1 gene mutation clinical feature prognosis

Received: 28 August 2020

PACS:

R733.71

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	LUO Liqing
	CAO Yuezhen
	PENG Zhenyi

Cite this article:

LUO Liqing,CAO Yuezhen,PENG Zhenyi. Clinical characteristics and prognostic analysis in acute myeloid leukemia with isocitrate dehydrogenase 1 gene mutation[J]. 滨州医学院学报, 2021, 44(2): 104-107.

URL:

http://manu58.magtech.com.cn/Jwk_bzyxy/EN/10.19739/j.cnki.issn1001-9510.2021.02.006 OR http://manu58.magtech.com.cn/Jwk_bzyxy/EN/Y2021/V44/I2/104

[1] 孙洪坤,王丽君,王娇婷,等.血清胸苷激酶1与急性白血病的相关研究分析[J].滨州医学院学报,2019,42(2):135-137.
[2] 张强.GALNT12对急性髓系白血病细胞生长影响的研究[J].滨州医学院学报,2017,40(2):117-119.
[3] SWERDLOW S H, CAMPOO E, HARRIS N L, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues[M].4thed.Lyon:IARC,2008.
[4] MARDIS E R,DING L,DOOLING D J,et a1.Recurring mutations found by sequencing an acute myeloid leukemia genome[J].N Engl J Med,2009,361(11):1058-1066.
[5] 王蓉娴,吴德沛,陈苏宁,等.急性髓系白血病患者IDHl及IDH2基因突变及临床特征分析[J].中华医学杂志,2013,93(10):751-755.
[6] 罗丽卿,彭振翼,司秀文,等.急性髓细胞白血病IDH基因突变临床特征及预后意义[J].中华肿瘤防治杂志,2017,24(21):1530-1533.
[7] AL-KHALLAF H. Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight[J]. Cell Biosci, 2017, 7: 37.
[8] 贾祝霞,周民,晁红颖,等.急性髓系白血病患者IDHl和IDH2基因突变分析[J].中华血液学杂志,2012,33(5):397-401.
[9] CHAO H Y, JIA Z X, CHEN T, et al . IDH2 mutations are frequent in Chinese patients with acute Myeloid leukemia and associated with NPM1 mutations and FAB-M2 subtype[J]. International Journal of Laboratory Hematology, 2012,34(5):502–509.
[10] 商臻,王迪,肖敏,等.205例急性髓系白血病患者IDH1基因突变的检测及其临床意义分析[J].中国实验血液学杂志,2012,20(6):1307-1311.
[11] 魏计锋,仇惠英,陈广华,等.急性髓系白血病患者IDH1基因突变及其临床意义[J].中国实验血液学杂志,2015,23 (5 ) :1252-1257.
[12] IM A P, SEHGAL A R, CARROLL M P, et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies[J].Leukemia, 2014,28(9) :1774-1783.
[13] SHUNICHIRO Y, EISAKU I, KENJI T, et al. IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation[J]. European Journal of Haematology,2014,92(6) :471-477.
[14] KOSZARSKA M,BORS A,FECZKO A,et al.Type and location of isocitrate dehydrogenase mutations influence clinical characteristics and disease outcome of acute myeloid leukemia[J]. Leuk Lymphoma,2013,54( 5) :1028-1035.
[15] POPOVICI-MULLER J, LEMIEUX R M, ARTIN E, et al. Discovery of AG-120(Ivosidenib): a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers[J]. ACS Med Chem Lett, 2018, 9(4): 300-305.
[16] BODDU P, BORTHAKUR G. Therapeutic targeting of isocitrate dehydrogenase mutant AML[J]. Exp Opin Investig Drugs, 2017, 26(5): 525-530.