A mutational and expressional analysis of <i>DNMT3A</i> in acute myeloid leukemia cytogenetic subgroups

Zare‐Abdollahi, Davood; Safari, Shamsi; Movafagh, Abolfazl; Riazi-Isfahani, Sahand; Ghadyani, Mojtaba; Hashemi‐Gorji, Feyzollah; Nasrollahi, Mohammad Foad; Omrani, Mir Davood

doi:10.1179/1607845415y.0000000001

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…Adult patients’ ( n = 128) in the range of 16–60 years, for whom diagnostic peripheral blood (PB) ( n = 76 with blast ≥30%) or bone marrow (BM) ( n = 52), samples were available and were included after obtaining Institutional Review Board approval and informing consent in accordance with the Declaration of Helsinki. Because of common treatment and to have a larger sample size, samples from previous studies were included . The patients were classified according to the French–American–British (FAB) Cooperative Group Criteria .…”

Section: Methodsmentioning

confidence: 99%

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Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

Zare‐Abdollahi

Safari

Movafagh

et al. 2016

Int J Lab Hematology

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Section: Methodsmentioning

confidence: 99%

“…Total RNA extraction and complementary DNA (cDNA) synthesis were performed as described previously . In this study, we established qRT‐PCR using primers dedicated to the sensitive detection of BECN1 mRNA (accession no.…”

Section: Methodsmentioning

confidence: 99%

Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

Zare‐Abdollahi

Safari

Movafagh

et al. 2016

Int J Lab Hematology

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“…These normal cytogenetic patients with isolated bi-allelic CEBPA (biCEBPA) or NPM1 mutation without FLT3-ITD are associated with a favorable prognosis, whereas FLT3-ITD or TP53 mutations are associated with a poor prognosis (3)(4)(5)(6). DNA methyltransferase 3A (DNMT3A) gene mutations are associated with hyperleukocytosis at disease presentation, the elderly, and a poor prognosis (7). Patients less than 60 years and with DNMT3A, FLT3-ITD, and NPM1 mutations had a shorter event-free survival (EFS) (P=0.047).…”

Section: Introductionmentioning

confidence: 99%

ND4 mutations are more prevalent in patients with acute myeloid leukemia of M2 morphology

Xu¹,

Zhao²,

Zhu³

et al. 2018

Transl. Cancer Res

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Background: To evaluate the prognostic value of ND4 gene mutation and other gene mutations in acute myeloid leukemia (AML) patients, especially among those without karyotype abnormalities.Methods: We analyzed the biological and clinical characteristics of 460 newly diagnosed AML patients.The mutation status and prognostic impact in FLT3-ITD, NPM1, c-KIT, CEBPA, DNMT3A, and ND4 genes were investigated.Results: The frequency of ND4 gene mutation was 6.6%. ND4 mutations were prevalent in patients with AML of M2 morphology (P=0.001). About 11.3% patients were diagnosed with core binding factor (CBF) AML and c-KIT mutations were most commonly seen in CBF leukemia patients (16.2%). DNMT3A mutations were usually found in M5 but not in M4 (P=0.006 and 0.498, respectively). ND4 germline mutations in non-M3 patients included types of A131V, F149L, A404T, and Y409H, while one M3 patient had type of G242D somatic mutation. Patients with ND4 mutations were significantly associated with CD19 expression in non-M3 patients (P=0.045). Patients with ND4 germline mutations may have unfavorable survival, but showed no statistical significance in overall survival (OS) and relapse-free survival (RFS) between patients with germline ND4 mutations and wild-type (P=0.159 and 0.087, respectively). According to the molecular prognostic factors, patients with normal cytogenetic risk were divided into three groups in the OS and RFS analysis (P=0.017 and 0.025, respectively) as favorable mutational risk has favorable prognosis and unfavorable mutational risk has poor one.Conclusions: Conventional molecular and cytogenetic factors could divide AML patients into distinctive prognosis groups. ND4 mutations were prevalent in M2 patients and were associated with higher expression of CD19. Whether patients with germline ND4 mutations have poorer prognosis still needs to be confirmed.

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“…Recent studies have found that frequency of DNMT3A mutations in AML is 17%»30% and most of DNMT3A mutations are heterozygous 12,15,16,18 Besides Common DNMT3A R882 mutation, mutations of V897D, G543C and R478W are also found.…”

mentioning

confidence: 99%

“…20 Although there were many studies, there was no definite conclusion about effect of DNMT3A mutations on AML prognosis (Table 1). [15][16][17][18][19][20][21]26 FLT3 is the most frequently mutated gene in AML (Table 1), with an approximately 28%»34%of AML cases harboring FLT3 mutations 28,29 FLT3 have 2 kinds of mutations: an internal tandem duplication (ITD) in the juxtamembrane domain and a point mutation of the tyrosine kinase domain (TKD). Estimated 20-25% of AML cases harbor FLT3-ITD mutations, 27 and FLT3-ITDmutations in adult AML are associated with clinical features such as having higher white blood cell count and higher peripheral blood blast cell count.…”

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confidence: 99%

Chronic myelomonocytic leukemia with double-mutations in DNMT3A and FLT3-ITD treated with decitabine and sorafenib

Wang

Xiao

et al. 2017

Cancer Biology & Therapy

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Chronic myelomonocytic leukemia (CMML) is a heterogeneous neoplastic hematologic disorder with worse overall survival. Half of CMML have mutations, but case with concomitant mutations of DNA methyltransferase 3A (DNMT3A) and Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3-ITD) in CMML was not reported before. We reported a 51-year-old man who had CMML with concomitant mutations in DNMT3A and FLT3-ITD.The patient received decitabine and sorafenib combined treatment. In this report, we reviewed DNMT3A mutation and FLT3 mutation, and we reviewed treatment of decitabine and sorafenib. This report is significant. First: This is the first report on CMML with doublemutations of DNMT3A and FLT3-ITD. Second: It shows the importance of targeted drug in combined treatment of CMML.

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A mutational and expressional analysis of DNMT3A in acute myeloid leukemia cytogenetic subgroups

Cited by 7 publications

References 24 publications

Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

ND4 mutations are more prevalent in patients with acute myeloid leukemia of M2 morphology

Chronic myelomonocytic leukemia with double-mutations in DNMT3A and FLT3-ITD treated with decitabine and sorafenib

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