Genetic heterogeneity and clonal evolution in acute myeloid leukemia

Romer-Seibert, Jennifer S.; Meyer, Sara E.

doi:10.1097/moh.0000000000000626

Cited by 18 publications

(15 citation statements)

References 22 publications

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“…It is well-known that an approximate 45–55% of AML patients have sign of a chromosomal alteration and 95–96% have demonstrable genomic alterations. Probably, 100% of patients have such modifications, some of which have not yet been recognized [ 79 ].…”

Section: Mechanisms Of Benzene Carcinogenesismentioning

confidence: 99%

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Spatari

Allegra

Carrieri

et al. 2021

Cancers

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Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.

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Section: Mechanisms Of Benzene Carcinogenesismentioning

confidence: 99%

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Spatari

Allegra

Carrieri

et al. 2021

Cancers

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“…Acute myeloid leukemia (AML) is a heterogeneous class of diseases characterized by particularly high genetic instability that gives rise to multiple immunophenotypes in a single patient, rendering AML notoriously refractory to conventional immunotherapies (23). In attempt to circumvent this heterogeneity, Perna et al (24) performed meticulous proteomics and transcriptomics analysis of large surfaceome datasets from malignant and normal tissues, aiming at identifying antigen pairs which could serve as targets for combinatorial CAR therapy.…”

Section: Potential Logic Gate Inputs Antigenic Cuesmentioning

confidence: 99%

Section: Potential Logic Gate Inputsmentioning

confidence: 99%

Implementing Logic Gates for Safer Immunotherapy of Cancer

2021

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Targeting solid tumors with absolute precision is a long-standing challenge in cancer immunotherapy. The identification of antigens, which are expressed by a large fraction of tumors of a given type and, preferably, across various types, but not by normal cells, holds the key to developing safe, off-the-shelf immunotherapies. Although the quest for widely shared, strictly tumor-specific antigens has been the focus of tremendous effort, only few such candidates have been implicated. Almost all antigens that are currently explored as targets for chimeric antigen receptor (CAR) or T cell receptor (TCR)-T cell therapy are also expressed by healthy cells and the risk of on-target off-tumor toxicity has remained a major concern. Recent studies suggest that this risk could be obviated by targeting instead combinations of two or more antigens, which are co-expressed by tumor but not normal cells and, as such, are tumor-specific. Moreover, the expression of a shared tumor antigen along with the lack of a second antigen that is expressed by normal tissues can also be exploited for precise recognition. Additional cues, antigenic or non-antigenic ones, which characterize the tumor microenvironment, could be harnessed to further increase precision. This review focuses on attempts to define the targetable signatures of tumors and assesses different strategies employing advanced synthetic biology for translating such information into safer modes of immunotherapy, implementing the principles of Boolean logic gates.

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“…These mutations await confirmation of their relapse-specific nature in independent patient cohorts, as well as, in most cases, elucidation of their contributions to relapse-associated features. Other recent developments concern the investigation of mutational patterns at diagnosis and relapse of various cytogenetically or genetically determined AML subgroups [ 17 ], clonal evolution under targeted therapy [ 18 , 19 ], and the application of single-cell sequencing to the investigation of the evolution of AML from diagnosis to relapse [ 20 ].…”

Section: Genetic and Transcriptional Changes Between Diagnosis And Relapse Of Amlmentioning

confidence: 99%

Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A

Grandits

Wieser

2021

Experimental Hematology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Genetic heterogeneity and clonal evolution in acute myeloid leukemia

Cited by 18 publications

References 22 publications

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Implementing Logic Gates for Safer Immunotherapy of Cancer

Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A

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