scholarly journals DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Geórgia Muccillo Dexheimer ◽  
Jayse Alves ◽  
Laura Reckziegel ◽  
Gabrielle Lazzaretti ◽  
Ana Lucia Abujamra
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Epigenetic Modification ◽  
Dynamic Change ◽  
Cellular Transformation ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Acute Myeloid

During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome. Here, we report that distinct changes in DNA methylation may alter gene function and drive malignant cellular transformation during several stages of leukemogenesis. Most of these modifications occur at an early stage of disease and may predict myeloid/lymphoid transformation or response to therapy, which justifies its use as a biomarker for disease onset and progression. Methylation patterns, or its dynamic change during treatment, may also be used as markers for patient stratification, disease prognosis, and response to treatment. Further investigations of methylation modifications as therapeutic biomarkers, which may correlate with therapeutic response and/or predict treatment toxicity, are still warranted.

scholarly journals Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications

2019 ◽  
Vol 20 (18) ◽  
pp. 4576 ◽  
Author(s):  
Xianwen Yang ◽  
Molly Pui Man Wong ◽  
Ray Kit Ng
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Genetic Alterations ◽  
Dna Methyltransferases ◽  
Clinical Implications ◽  
Aberrant Dna Methylation ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a heterogeneous disease that is characterized by distinct cytogenetic or genetic abnormalities. Recent discoveries in cancer epigenetics demonstrated a critical role of epigenetic dysregulation in AML pathogenesis. Unlike genetic alterations, the reversible nature of epigenetic modifications is therapeutically attractive in cancer therapy. DNA methylation is an epigenetic modification that regulates gene expression and plays a pivotal role in mammalian development including hematopoiesis. DNA methyltransferases (DNMTs) and Ten-eleven-translocation (TET) dioxygenases are responsible for the dynamics of DNA methylation. Genetic alterations of DNMTs or TETs disrupt normal hematopoiesis and subsequently result in hematological malignancies. Emerging evidence reveals that the dysregulation of DNA methylation is a key event for AML initiation and progression. Importantly, aberrant DNA methylation is regarded as a hallmark of AML, which is heralded as a powerful epigenetic marker in early diagnosis, prognostic prediction, and therapeutic decision-making. In this review, we summarize the current knowledge of DNA methylation in normal hematopoiesis and AML pathogenesis. We also discuss the clinical implications of DNA methylation and the current therapeutic strategies of targeting DNA methylation in AML therapy.

scholarly journals Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy

2015 ◽  
Author(s):  
Mohammad Shahjahani ◽  
Elham Khodadi ◽  
Mohammad Seghatoleslami ◽  
Javad Mohammadi Asl ◽  
Neda Golchin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Genetic Alterations ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Cytogenetic Abnormalities ◽  
Myeloid Leukemias ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important diagnostic tools in diagnosis, classification and prognosis in acute myeloid leukemias. Based on World Health Organization (WHO) classification, acute myeloid leukemias can be divided to four groups. Due to the heterogeneous nature of AML and since most therapeutic protocols in AML are based on genetic alterations, gathering further information in the field of rare disorders as well as common cytogenetic abnormalities would be helpful in determining the prognosis and treatment in this group of diseases. Recently, the role of microRNAs (miRNAs) in both normal hematopoiesis and myeloid leukemic cell differentiation in myeloid lineage has been specified. miRNAs can be used instead of genes for AML diagnosis and classification in the future, and can also play a decisive role in the evaluation of relapse as well as response to treatment in the patients. Therefore, their use in clinical trials can affect treatment protocols and play a role in therapeutic strategies for these patients. In this review, we have examined rare cytogenetic abnormalities in different groups of acute myeloid leukemias according to WHO classification, and the role of miRNA expression in classification, diagnosis and response to treatment of these disorders has also been dealt with.

scholarly journals Myelodysplastic syndrome with myelofibrosis in a 12-year-old patient – A case report

2018 ◽  
Vol 26 (1) ◽  
pp. 95-103
Author(s):  
Andreea Oltean ◽  
Mihaela Ioana Chincesan ◽  
Oana Marginean ◽  
Emoke Horvath
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Case Report ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Cell Lineage ◽  
Response To Treatment ◽  
Hematopoietic Stem ◽  
Pediatric Clinic ◽  
Acute Myeloid

Abstract Myelodysplastic syndromes are a heterogeneous group of clonal disorders characterized by peripheral blood cytopenia and normal or hypercellular bone marrow with dysplasia in more than one blood cell lineage, unfavorable prognosis, and lack of response to treatment. We present the case of a 12-year-old male patient who was referred to the Hematology and Oncology Department of Pediatric Clinic I Târgu- Mures in May 2016, with splenomegaly and pancytopenia. The osteomedullary biopsy revealed myelofibrosis, discrete dysplasia of the myeloid series and megakaryocytes, blasts CD34+ approximately 10%, which led to the diagnosis of myelodysplastic syndrome with myelofibrosis. The myeloid precursors indicated a high risk of transformation into acute myeloid leukemia, so chemotherapy associated with corticosteroids was started, leading to slight improvements. Although myelodysplastic syndrome associated with myelofibrosis is rare at this age, despite the treatment and favorable progression in the case presented, in the absence of hematopoietic stem cell transplantation the prognosis remains unfavorable.

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