Clinical characteristics and prognostic analysis of acute myeloid leukemia patients with PTPN11 mutations

ABSTRACT

Objectives

Little is known about the clinical impact of germline/somatic mutations of PTPN11 in acute leukemia. The aim of this study was to investigate the clinical characteristics and prognostic impact of PTPN11 mutations in patients with acute myeloid leukemia (AML).

Methods:

Seventy-four patients with PTPN11 mutation-positive AML treated at our institution were enrolled in this study. The prevalence of PTPN11 mutations was examined using targeted next-generation sequencing technology, and patients with AML and PTPN11 mutations were screened. Clinical characteristics, prognostic impact, and association between PTPN11 mutations and other mutations were analyzed retrospectively.

Results:

PTPN11 mutations co-occurred more commonly with DNMT3A, NPM1, and FLT3 internal tandem duplication mutations. Compared with PTPN11 wild-type (WT) patients, PTPN11 mutation-positive AML patients presented with higher white blood cell (WBC) and platelet (PLT) counts. In 74 PTPN11 positive AML patients, PTPN11 mutations had an adverse effect on overall survival (OS) (62.5%) and a negative prognostic effect on event-free survival (EFS) (50%). Allo-hematopoietic stem cell transplantation (HSCT) abrogated the negative effect of mutations in PTPN11; the OS and EFS of AML patients with PTPN11 mutations who received transplantation were longer than those of AML patients with PTPN11 mutations who did not undergo allo-HSCT (P = 0.001, EFS; P < 0.001, OS). Discussion: Newly diagnosed PTPN11 mutation-positive AML patients with high WBC and PLT counts or presenting no remission after first induction chemotherapy suffer from high mortality rates.

Conclusion:

Given the lack of targeted therapies for PTPN11 mutations, timely HSCT is necessary for patients.

KEYWORDS:

• PTPN11 mutations
• acute myeloid leukemia
• secondary mutation
• prognosis factor

Acknowledgments and funding

This study was supported by grant from the National Key R&D Program of China (2019YFA0111000), the National Natural Science Foundation of China (82100170, 82000158), the Natural Science Foundation of the Jiangsu Higher Education Institution of China (18KJB320019), the Natural Science Foundation of Jiangsu Province (BK20210087), priority academic program development of Jiangsu Higher Education Institution, the Innovation Capability Development Project of Jiangsu Province (BM215004), the Open Project of Jiangsu Biobank of Clinical Resources (SBK202003001, SBK202003003), Jiangsu Provincial Key Medical Center (YXZXA2016002) and National Science and Technology Major Project (2017ZX09304021). All the samples were from Jiangsu Biobank of Clinical Resources.

Data availability statement

The data that supports the findings of this study are available in the supplementary material of this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by National Natural Science Foundation of China: [Grant Number 82000158]; National Natural Science Foundation of China: [Grant Number 82100170]; Natural Science Foundation of Jiangsu Province: [Grant Number BK20210087].