Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis

Abstract

BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7.4%). Among cases aged 65 years or below that were also FLT3-ITD-negative and in the intermediate cytogenetic prognosis group, BCOR or BCORL1 gene mutations were observed in 11% of cases (12 of 111 cases), and this group had significantly lower 5-year overall survival (OS) (13.6% vs. 55.0%, P = 0.0021) and relapse-free survival (RFS) (14.3% vs. 44.5%, P = 0.0168) compared to cases without BCOR or BCORL1 gene mutations. Multivariate analysis demonstrated that BCOR mutations were an independent unfavorable prognostic factor (P = 0.0038, P = 0.0463) for both OS and RFS. In cases of AML that are FLT3-ITD-negative, aged 65 years or below, and in the intermediate cytogenetic prognosis group, which are considered to have relatively favorable prognosis, BCOR gene mutations appear to be an important prognostic factor.

Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

“…In 2011, we discovered recurrent loss-of-function mutations of BCOR in AML (about 4% of cases with normal karyotype) and found that they were usually mutually exclusive of FLT3-ITD and NPM1 mutations, co-occurred with DNA methyl transferase (DNMT3A) mutations and were associated with a poor outcome [9]. Our findings have been subsequently confirmed by other investigators both in AML and MDS [10][11][12][13][14]. Interestingly, one study on Japanese patients reported a preferential co-occurrence of BCOR mutations with K-RAS, N-RAS, and RUNX1 mutations [11].…”

“…Interestingly, one study on Japanese patients reported a preferential co-occurrence of BCOR mutations with K-RAS, N-RAS, and RUNX1 mutations [11]. BCOR 1 ligand (BCORL1) gene has been also found to be mutated in 3.7-6% of AML patients [11,15].…”

Spontaneous Remission in a Patient With Acute Myeloid Leukemia Leading to Undetectable Minimal Residual Disease

“…Uniquely, our patient had resolution of his previous BCOR, RUNX1, and IDH2 mutations on the NGS panel. BCOR and RUNX1 mutations are both adverse prognostic markers and are associated with higher risk disease in AML, whereas IDH2 mutations are generally thought to have a neutral impact but have become more clinically relevant recently with the discovery of novel IDH1/2 inhibitors [16][17][18]. To our knowledge, resolution of BCOR, RUNX1, or IDH2 mutations has not been described in previous case reports of SR in AML; however, monitoring of RUNX1 and IDH2 mutation status by NGS during CR has been shown to identify patients at risk of relapse [19][20][21].…”

BCOR Involvement in Cancer

“…NGS techniques allow for the identification of new molecular subgroups potentially related to specific clinical characteristics, in addition to those already identifiable by cytogenetic studies. In the context of these specific entities, association with BCOR comutations (Table 2) is particularly relevant in the following instances: intermediate cytogenetic prognosis and FLT3–ITD-negative AML in adult patients under 65 [89], nonselected myeloid neoplasms with mutations in cohesin-coding genes [95], AML with changes associated with myelodysplasia [92], AML with trisomy 11 or 13 [99,100], AML with balanced or unbalanced chromosomal rearrangements [97], AML with normal karyotype [97,98,107] (in particular, pediatric AML) [88] or if co-occurring mutations in NPM1, CEBPA, FLT3-ITD, MLL-PTD or RUNX1 are present [105,107,117].…”