Mutation in TET2 or TP53 predicts poor survival in patients with myelodysplastic syndrome receiving hypomethylating treatment or stem cell transplantation

Abstract

Recent molecular studies identified genetic mutations in myelodysplastic syndrome (MDS) and their associations with clinical parameters. 1,2 As an increasing number of recurrent somatic mutations have been found, many investigators are focusing on genetic mutations as candidate molecular markers for MDS prognosis and treatment outcomes, especially following hypomethylating treatment (HMT) or stem cell transplantation (SCT). In this study, we analyzed recurrent TET2, TP53, ETV6, RUNX1, EZH2, ASXL1, SF3B1, U2AF1 and SRSF2 mutations, which are relatively frequent, and their influence on survival was reported independently of clinical parameters. 2,3 Fifty-two patients receiving HMT and/or SCT for MDS at our institution from April 2009 to May 2011 Abbreviations: ANC = absolute neutrophil count; HMT = hypomethylating treatment; IPSS = international prognostic scoring system; MAC = myeloablative conditioning; MUD = matched unrelated donor; MSD = matched sibling donor; RARS = refractory anemia with ringed sideroblasts; RAEB = refractory anemia with excess blast; RBC = red blood cell; RCMD = refractory cytopenia with multilineage dysplasia; RIC = reduced-intensity conditioning; SCT = stem cell transplantation; WBC = white blood cell; WHO = World Health Organization.

Prognostic role of TET2 deficiency in myelodysplastic syndromes: A meta-analysis

“…After carefully reading the full texts, 23 studies were eliminated due to insufficient data. Ultimately, 14 studies [12, 15, 16, 20–30] including an article [29] and a letter to the editor [20] were obtained and included in the meta-analysis.…”

“…Scopim-Ribeiro et al (2015) [22] included patients with both de novo AML and MDS, however, only patients with MDS were included in the meta-analysis. The median age in the eight studies [12, 15, 16, 22, 23, 25–27] was older than 60 years old, the median age was younger than 60 years old in four studies [20, 21, 24, 28] and the median age was not available in the other two studies [29, 30]. Patients in 10 eligible studies [12, 14, 20–27] were classified by WHO criteria, patients in 3 studies [28–30] were classified by FAB criteria and patients in KOSMIIDER et al (2009) [16] were classified by both WHO and FAB criteria.…”

“…O.Kosmider et al (2009a) [15] suggested that TET2 mutations were frequent adverse events in CMML. SMITH et al (2010) [12] reported that TET2 mutations had no prognostic value on patients with MDS and CMML and Kim et al (2015) [20] indicated that TET2 mutations were poor prognostic factor in patients with MDS. Hence, to gain full insight into the prognostic value of TET2 mutations in patients with MDS, we performed this meta-analysis.…”

Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts

“…Thus, marrow response, PB blast detection, and karyotyping may be useful for selecting pre-HSCT treatment option and patients who are most appropriate for HSCT. Mutations in certain genes may be useful for prediction of posttransplantation survival, particularly in patients with complex karyotypes (e.g., by assessing TP53 ) [41, 42], although these markers require further studies for prediction of HMT response [39, 43–45]. Future clinical trial might be useful for developing and evaluating a stepwise decision-making model that is based on these risk factors.…”

TET2 and MEG3 promoter methylation is associated with acute myeloid leukemia in a Hainan population

“…Mutations in TET2 have been observed in a variety of myeloid disorders [23]. Subsequent sequencing analysis revealed that TET2 mutations are present in approximately 7%−23% of AML patients [24–26] and in 14%−55% of patients with other myeloid malignancies [23, 24, 27]. Reduced TET2 activity and 5-hydroxymethylcytosine (5hmC) levels were observed in AML, MDS, chronic myelomonocytic leukemia (CMML), lymphoid leukemia, and other patients with hematological malignancies.…”