伴有骨髓发育异常相关改变的急性髓系白血病与原发性急性髓系白血病之间不同的突变图谱

Distinct Mutation Landscapes Between Acute Myeloid Leukemia With Myelodysplasia-Related Changes and De Novo Acute Myeloid Leukemia.

作者信息

Gao Yajuan, Jia Mingnan, Mao Yueying, Cai Hao, Jiang Xianyong, Cao Xinxin, Zhou Daobin, Li Jian

机构信息

Hematology, Beijing, China.

Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Am J Clin Pathol. 2022 May 4;157(5):691-700. doi: 10.1093/ajcp/aqab172.

DOI:10.1093/ajcp/aqab172

PMID:34664628

Abstract

OBJECTIVES

To explore the distinct mutation profiles between acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and de novo AML and their relationships with prognosis.

METHODS

Next-generation sequencing of 42 myeloid neoplasm-related genes in 293 newly diagnosed patients with AML.

RESULTS

Eighty-four patients had AML-MRC, and 161 patients had de novo AML. The mutation rates of ASXL1 (25% vs 8.7%, P = .001), NRAS (17.9% vs 8.1%, P = .022), PTPN11 (11.9% vs 5%, P = .048), SETBP1 (6% vs 0.6%, P = .033), SRSF2 (11.9% vs 5.6%, P = .08), TP53 (16.7% vs 1.2%, P < .001), and U2AF1 (17.9% vs 7.5%, P = .014) in AML-MRC were higher than those in de novo AML, while the rates of FLT3-ITD (3.6% vs 15.5%, P = .005), KIT (0% vs 6.2%, P = .046), WT1 (3.6% vs 9.9%, P = .077), NPM1 (1.2% vs 21.7%, P < .001), and CEBPA (4.8% vs 24.2%, P < .001) mutation were lower. The appearance of ASXL1, TP53, U2AF1, SRSF2, and SETBP1 mutation could predict AML-MRC-like features in de novo AML, which was related to older age (60 vs 51 years, P = .001), low WBC counts (4.7 × 109/L vs 11.6 × 109/L, P = .001), and inferior outcomes (median overall survival, 15 months vs not reached, P = .003).

CONCLUSIONS

The presence of AML-MRC-related mutations can reveal a subset of patients with de novo AML similar to patients with AML-MRC.

摘要

目的

探讨伴有骨髓增生异常相关改变的急性髓系白血病（AML-MRC）与初发AML之间不同的突变谱及其与预后的关系。

方法

对293例新诊断的AML患者进行42个髓系肿瘤相关基因的二代测序。

结果

84例患者为AML-MRC，161例患者为初发AML。AML-MRC中ASXL1（25%对8.7%，P = 0.001）、NRAS（17.9%对8.1%，P = 0.022）、PTPN11（11.9%对5%，P = 0.048）、SETBP1（6%对0.6%，P = 0.033）、SRSF2（11.9%对5.6%，P = 0.08）、TP53（16.7%对1.2%，P < 0.001）和U2AF1（17.9%对7.5%，P = 0.014）的突变率高于初发AML，而FLT3-ITD（3.6%对15.5%，P = 0.005）、KIT（0%对6.2%，P = 0.046）、WT1（3.6%对9.9%，P = 0.077）、NPM1（1.2%对21.7%，P < 0.001）和CEBPA（4.8%对24.2%，P < 0.001）突变率较低。ASXL1、TP53、U2AF1、SRSF2和SETBP1突变的出现可预测初发AML中类似AML-MRC的特征，这与年龄较大（60岁对51岁，P = 0.001）、白细胞计数低（4.7×10⁹/L对11.6×10⁹/L，P = 0.001）及预后较差（中位总生存期，15个月对未达到，P = 0.003）相关。