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CSF3R Mutations are frequently associated with abnormalities of RUNX1, CBFB, CEBPA, and NPM1 genes in acute myeloid leukemia
Author(s) -
Zhang Yang,
Wang Fang,
Chen Xue,
Zhang Yu,
Wang Mingyu,
Liu Hong,
Cao Panxiang,
Ma Xiaoli,
Wang Tong,
Zhang Jianping,
Zhang Xian,
Lu Peihua,
Liu Hongxing
Publication year - 2018
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31586
Subject(s) - cebpa , npm1 , myeloid leukemia , medicine , runx1 , leukemia , cancer research , core binding factor , missense mutation , myeloid , gene , mutation , immunology , biology , transcription factor , genetics , karyotype , chromosome
Background Mutations in the colony‐stimulating factor 3 receptor ( CSF3R ) gene occur frequently in chronic neutrophilic leukemia and are rare in de novo acute leukemia. The objective of this study was to assess the incidence of CSF3R mutations in acute leukemia and their association with other genetic abnormalities. Methods Amplicon‐targeted, next‐generation sequencing of 58 genes was performed retrospectively on 1152 patients (acute myeloid leukemia [AML], n = 587; acute lymphoid leukemia [ALL], n = 565). Reverse transcriptase‐polymerase chain reaction analysis was used to detect 35 leukemia‐specific gene fusions. Results CSF3R mutations (26 patients) were detected in 3.6% (13 of 364 patients), 4.6% (8 of 175 patients), and 8.3% (4 of 48 patients) of those with de novo, relapsed, and secondary AML, respectively, and in 0.2% (1 of 565 patients) of those with ALL. In total, 9 distinct CSF3R mutations were detected. Membrane‐proximal missense mutations and cytoplasmic truncations were identified as mutually exclusive. The proportion of patients who had French‐American‐British subtypes M2 and M4 in the CSF3R ‐mutated group was significantly greater than that in the CSF3R wild‐type group for both the de novo AML cohort ( P = .001) and the relapsed AML cohort ( P = .024). All de novo and relapsed AMLs with CSF3R mutations were associated with genetic alterations in transcription factors, including RUNX1‐RUNX1T1, CBFB‐MYH11 , double‐mutated CCAAT/enhancer binding protein α ( CEBPA dm), and NPM1 mutations; and core‐binding factor gene abnormalities and CEBPA dm accounted for 90.5% (19 of 21 patients). Conclusions CSF3R mutations are uncommon in AML; however, when they occur, they are often associated with core‐binding factor gene abnormalities and CEBPA dm. An in‐depth understanding of the interaction between these genetic alterations could facilitate a clearer understanding of the role of CSF3R mutations in AML development and may be used for disease classification, prognosis, and the development of targeted therapy.