Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges

Shallis, Rory M.; Wang, Rong; Davidoff, Amy J.; Ma, Xiaomei

doi:10.1016/j.blre.2019.04.005

Cited by 637 publications

(463 citation statements)

References 181 publications

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“…Acute myeloid leukemia (AML) is a highly heterogeneous disease in adults that is fatal in the majority of patients (1). It is estimated that only 15%-40% of patients achieve long-term survival with current approaches, which include genetic risk stratification and allogeneic stem-cell transplantation (SCT) for intermediate-high risk subjects (2,3). Although toxicity is a major concern when treating AML in adults, the high refractoriness and rate of relapse seems to be the leading cause of death, even in developing countries (4,5).…”

Section: ' Introductionmentioning

confidence: 99%

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

Silva¹,

Rosa²,

Seguro³

et al. 2020

Clinics

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OBJECTIVES: The outcomes of refractory and relapsed acute myeloid leukemia (AML) patients in developing countries are underreported, even though the similar classic regimens are widely used. METHODS: We conducted a retrospective comparison of ''MEC'' (mitoxantrone, etoposide, and cytarabine) and ''FLAG-IDA'' (fludarabine, cytarabine, idarubicin, and filgrastim) in adults with first relapse or refractory AML. RESULTS: In total, 60 patients were included, of which 28 patients received MEC and 32 received FLAG-IDA. A complete response (CR) rate of 48.3% was observed. Of the included patients, 16 (27%) died before undergoing bone marrow assessment. No statiscally significant difference in CR rate was found between the two protocols (p=0.447). The median survival in the total cohort was 4 months, with a 3-year overall survival (OS) rate of 9.7%. In a multivariable model including age, fms-like tyrosine kinase 3 (FLT3) status, and stem-cell transplantation (SCT), only the last two indicators remained significant: FLT3-ITD mutation (hazard ratio [HR] =4.6, po0.001) and SCT (HR=0.43, p=0.01). CONCLUSION: In our analysis, there were no significant differences between the chosen regimens. High rates of early toxicity were found, emphasizing the role of supportive care and judicious selection of patients who are eligible for intensive salvage therapy in this setting. The FLT3-ITD mutation and SCT remained significant factors for survival in our study, in line with the results of previous studies.

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Section: ' Introductionmentioning

confidence: 99%

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

Silva¹,

Rosa²,

Seguro³

et al. 2020

Clinics

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“…Current therapies, such as chemotherapy and allogeneic stem cell transplantation, for AML are commonly effective a limited population of younger and fit patients, but the majority of elder individuals suffer from unfavorable prognosis and low survival [1,24]. Well-documented evidence exists proving that multiple miRNAs have a critical role to play in orchestrating leukemia cell proliferation and apoptosis, which may potentially be used as therapeutic biomarkers [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Acute myeloid leukemia (AML) represents a malignant disorder originating in the bone marrow, which has been recognized to cause clonal spread as well as differentiation arrest of myeloid progenitor cells [1]. It is a heterogeneous disease accompanied by a warning mortality, where the prognosis status is dependent on cytogenetic and molecular changes as well as patient-related situations, such as age, and complications [2,3].…”

Section: Introductionmentioning

confidence: 99%

SPOP accelerates acute myeloid leukemia initiation and development through miR-183-mediated METAP2 inhibition

Sun

et al. 2020

Preprint

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Background: Recent miRNA profiling studies have implicated the potential use of miRNAs as as diagnostic and prognostic indicators in acute myeloid leukemia (AML), which has been reportedly implicated in the interplay with certain mRNAs. Herein this study, we intend to characterize the functional relevance of SPOP/miR-183/METAP2 axis in AML in vivo and in vitro. Methods: Differentially expressed mRNAs and downstream regulatory miRNA were predicted by in silico analysis. We induced SPOP/miR-183/METAP2 overexpression or inhibition to examine their effects on AML cell proliferation and apoptosis in vitro and tumor growth in vivo , along with their interaction with β-catenin. Results: SPOP and miR-183 were highly expressed, while METAP2 was poorly expressed in patient peripheral blood samples and cell lines of AML. SPOP accelerated the proliferation of AML cells and repressed apoptosis. Mechanistically, SPOP enhanced β-catenin protein stability and nuclear translocation leading to upregulated expression of miR-183. MiR-183 facilitated proliferation and inhibited apoptosis of AML cells by targeting METAP2. Furthermore, miR-183 inhibition and METAP2 overexpression reversed SPOP-induced AML cell malignancy. Besides, in vitro findings were reproduced by in vivo findings. Conclusion: SPOP stimulated AML malignant progression by inducing β-catenin stability and miR-183/METAP2 axis activation, highlighting a potential therapeutic target against AML recurrence and metastasis.

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“…It accounts for 20% of all hematological malignancy related deaths, with a 5‐year survival rate of 40% for younger patients (18‐60 years) and 5‐year survival rate of 10% for the elder patients (age above 60 years) . Despite there are potentially curative treatments for AML patients, including intensive chemotherapy and allogeneic stem cell transplantation, only a minority of eligible AML patients would benefit from these therapies, and half of patients received transplantation finally relapse . Hence, it is needed to explore novel biomarkers for diagnosis, disease progression, and prognosis of AML, so as to conduct effective surveillance and therapies of AML patients at early stage.…”

Section: Introductionmentioning

confidence: 99%

Identification of A‐kinase interacting protein 1 as a potential biomarker for risk and prognosis of acute myeloid leukemia

Yan¹,

Li²,

Gao³

2020

Clinical Laboratory Analysis

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to investigate the correlation of A-kinase interacting protein 1 (AKIP1) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML).Methods: 291 de novo AML patients and 97 controls were consecutively recruited, and bone marrow samples were collected to detect AKIP1 expression using quantitative polymerase chain reaction prior to initial treatment. Treatment response, eventfree survival (EFS), and overall survival (OS) in AML patients were evaluated. Results:A-kinase interacting protein 1 expression was higher in AML patients than that in controls; meanwhile, receiver operating characteristic curve displayed that AKIP1 was able to distinguish AML patients from controls (area under the curve:0.772, 95%CI: 0.720-0.823). Among AML patients, AKIP1 high expression was correlated with −7 or 7q−, monosomal karyotype, and worse risk stratification. Moreover, AKIP1 expression was negatively correlated with complete remission achievement, while no correlation of AKIP1 expression with hematopoietic stem cell transplantation achievement was observed. AKIP1 high expression was associated with shorter EFS and OS in total patients, and further subgroup analysis exhibited that AKIP1 high expression correlated with worse EFS and OS in intermediate-risk and poor-risk patients but not in better-risk patients. Besides, subsequent analysis revealed that AKIP1 high expression was an independent factor predicting unfavorable EFS and OS. Conclusion:A-kinase interacting protein 1 has the potential to be a novel marker for assisting AML management. K E Y W O R D S acute myeloid leukemia, A-kinase interacting protein 1, risk stratification, survival 1 | INTRODUC TI ON Acute myeloid leukemia (AML), an aggressive hematological malignancy, is characterized by abnormal cell proliferation and differentiation of the immature myeloid cells. 1,2 It accounts for 20% of all hematological malignancy related deaths, with a 5-year survival rate of 40% for younger patients (18-60 years) and 5-year survival rate of 10% for the elder patients (age above 60 years). 3-5 Despite there are potentially curative treatments for AML patients, including intensive chemotherapy and allogeneic stem cell transplantation, How to cite this article: Yan Y, Li X, Gao J. Identification of A-kinase-interacting protein 1 as a potential biomarker for risk and prognosis of acute myeloid leukemia. J Clin Lab Anal.

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Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges

Cited by 637 publications

References 181 publications

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

Salvage treatment for refractory or relapsed acute myeloid leukemia: a 10-year single-center experience

SPOP accelerates acute myeloid leukemia initiation and development through miR-183-mediated METAP2 inhibition

Identification of A‐kinase interacting protein 1 as a potential biomarker for risk and prognosis of acute myeloid leukemia

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