Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics

Ghanem, Hady; Tank, Niki; Tabbara, Imad A.

doi:10.1002/ajh.22197

Cited by 24 publications

(23 citation statements)

References 143 publications

(212 reference statements)

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“…Clonal chromosome alterations and fusion genes were firstly recognized, and were regarded as the most potent biomarkers for AML therapeutic response and survival prognosis (1). Subsequently, several gene mutations, including FLT3-internal tandem duplication, FLT3-tyrosine kinase domain, DNA methyltransferase 3α, isocitrate dehydrogenase and CCAAT/enhancer binding protein α mutations, have been identified to participate in the abnormal proliferation of leukemia progenitor cells or impaired differentiation (2)(3)(4). In addition, they have been identified as valuable prognostic biomarkers that affect the therapeutic regimen decision (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, several gene mutations, including FLT3-internal tandem duplication, FLT3-tyrosine kinase domain, DNA methyltransferase 3α, isocitrate dehydrogenase and CCAAT/enhancer binding protein α mutations, have been identified to participate in the abnormal proliferation of leukemia progenitor cells or impaired differentiation (2)(3)(4). In addition, they have been identified as valuable prognostic biomarkers that affect the therapeutic regimen decision (2)(3)(4). However, the aforementioned gene alterations alone have not fully elucidated the pathogenesis of AML, thus, current studies have focused on identifying novel biomarkers.…”

Section: Introductionmentioning

confidence: 99%

“…However, the aforementioned gene alterations alone have not fully elucidated the pathogenesis of AML, thus, current studies have focused on identifying novel biomarkers. The majority of studies have focused on the nuclear genome (2)(3)(4)(5), with less focus on the extranuclear genome (mitochondrial genome).…”

Section: Introductionmentioning

confidence: 99%

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Sequence variations of mitochondrial DNA D‑loop region in patients with acute myeloid leukemia

Zhou

Gou

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to explore variations of the displacement (D)-loop region in patients with acute myeloid leukemia (AML) and their possible associations with AML pathogenesis. Blood or bone marrow samples from 216 patients with AML (158 AML patients in the first stage, and 58 more patients with AML-M3 for further verification), and 146 healthy controls were collected. Sanger sequencing was performed for the D-loop region ranging between nucleotide (nt)15811 and nt 775. With the exception of mitochondrial microsatellite instability (mtMSI) variations, a total of 2,630 variations in 232 loci were identified with similar variation rates/person in patients with AML and controls when compared with the revised Cambridge reference sequence (8.54±2.14 vs. 8.77±2.15; P=0.366). A positive association between AML and variation-T152C was identified, which occurred more frequently in patients with AML compared with in controls [26.6 vs. 17.1%; P=0.048; odds ratio (OR), 1.752; 95% confidence interval (CI), 1.004-3.058]. Furthermore, T152C was identified to be associated with promyelocytic leukemia-retinoic acid receptor α(PML-RARα) and French-American-British AML subtypes, with a tendency to occur in patients with AML-M3. The AML-M3 sample size was extended by 58 cases, and it was identified that the T152C variation rate was significantly higher in patients with AML-M3 compared with that of controls (41.0 vs. 17.1%; P<0.001; OR, 3.228; 95% CI, 1.714-6.079). However, no association was identified between the T152C variation and clinical characteristics, or chemotherapy response in patients with AML-M3. In addition, the mtMSIs, including D310, mt514-523 (CA) n and T16189C, demonstrated no association with AML risk. Together, the results of the present study suggest that the mitochondrial DNA D-loop region is high variable, and that T152C is associated with AML risk, particularly regarding the M3 subtype. T152C mayparticipate in AML pathogenesis and may be a diagnostic biomarker; however further studies with larger sample sizes are required in order to verify its value.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sequence variations of mitochondrial DNA D‑loop region in patients with acute myeloid leukemia

Zhou

Gou

et al. 2017

Oncol Lett

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“…There are many advances in the treatments of leukemia and lymphoma in recent years, but the overall survival for patients with leukemia or lymphoma has not been improved obviously [1,2]. Identification of prognostic factors for leukemia or lymphoma is very helpful for clinicians to choose best therapeutic strategies for patients and improve their prognosis [2,][4]. In addition, identification of prognostic factors for leukemia or lymphoma is also helpful for us to get a better understanding of the pathogenesis of leukemia and lymphoma.…”

Section: Introductionmentioning

confidence: 99%

Serum 25-Hydroxyvitamin D Levels and Prognosis in Hematological Malignancies: A Systematic Review and Meta-Analysis

Wang

Guang-yun

et al. 2015

Cell Physiol Biochem

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Background/Aims: Serum 25-hydroxyvitamin D [25(OH)D] levels proved to be associated with prognosis of patients with colorectal cancer or breast cancer, but its prognostic role in hematological malignancies was still unclear. A systematic review and meta-analysis was performed to comprehensively evaluate the association between serum 25(OH)D levels and prognosis of patients with hematological malignancies. Methods: We searched Pubmed, Embase, Web of Science, and Google Scholar for studies evaluating the association between serum 25(OH)D levels and prognosis of patients with hematological malignancies. The hazard ratios (HR) with 95% confidence intervals (95%CI) for overall survival (OS) or relapse-free survival (RFS) were pooled using meta-analysis. Results: Seven studies with a total of 2,643 patients with hematological cancer were finally included into the meta-analysis. Overall, compared with normal serum 25(OH)D levels, low serum 25(OH)D levels were significantly associated with both poorer OS (HR = 1.85, 95% CI 1.54-2.23, P <0.001) and poorer RFS (HR = 1.45, 95% CI 1.25 to 1.70, P <0.001) in hematological malignancies. Subgroup analysis further showed that low serum 25(OH)D levels were significantly associated with poorer OS and RFS in both lymphoma and leukemia. Conclusion: Low serum 25(OH)D levels are significantly associated with poorer prognosis in patients with hematological malignancies including lymphoma and leukemia.

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“…Acute myeloid leukemia (AML) is a heterogeneous group of malignancies and improvements in the understanding of leukemogenesis are largely owing to the characterization of a large number of new mutations and gene amplifications during the last decade [1][2][3]. Novel high-resolution approaches such as array-based comparative genomic hybridization (aCGH) have also been used to determine copy number (CN) alterations in AML, and candidate genes have been proposed [4,5].…”

Section: Introductionmentioning

confidence: 99%

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

et al. 2013

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On behalf of the French ALFA groupGermline heterozygous alterations of the tumor-suppressor gene neurofibromatosis-1 (NF1) lead to neurofibromatosis type 1, a genetic disorder characterized by a higher risk to develop juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML). More recently, somatic 17q11 deletions encompassing NF1 have been described in many adult myeloid malignancies. In this context, we aimed to define NF1 involvement in AML. We screened a total of 488 previously untreated de novo AML patients for the NF1 deletion using either array comparative genomic hybridization (aCGH) or real-time quantitative PCR/fluorescence in situ hybridization approaches. We also applied massively parallel sequencing for in depth mutation analysis of NF1 in 20 patients including five NF1-deleted patients. We defined a small~0.3 Mb minimal deleted region involving NF1 by aCGH and an overall frequency of NF1 deletion of 3.5% (17/485). NF1 deletion is significantly associated with unfavorable cytogenetics and with monosomal karyotype notably. We discovered six NF1 variants of unknown significance in 7/20 patients of which only one out of four disappeared in corresponding complete remission sample. In addition, only one out of five NF1-deleted patients has an acquired coding mutation in the remaining allele. In conclusion, direct NF1 inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression. Am. J.

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Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics

Cited by 24 publications

References 143 publications

Sequence variations of mitochondrial DNA D‑loop region in patients with acute myeloid leukemia

Sequence variations of mitochondrial DNA D‑loop region in patients with acute myeloid leukemia

Serum 25-Hydroxyvitamin D Levels and Prognosis in Hematological Malignancies: A Systematic Review and Meta-Analysis

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

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