scholarly journals Gene Mutations as Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia

2017 ◽  
Vol 8 ◽  
Author(s):  
Habsah Aziz ◽  
Chow Y. Ping ◽  
Hamidah Alias ◽  
Nurul-Syakima Ab Mutalib ◽  
Rahman Jamal
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Therapeutic Targets ◽  
Gene Mutations ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Genomic Abnormalities as Biomarkers and Therapeutic Targets in Acute Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5055
Author(s):  
Sara Ribeiro ◽  
Anna M. Eiring ◽  
Jamshid S. Khorashad
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Therapeutic Targets ◽  
Gene Mutations ◽  
Functional Methods ◽  
Stem And Progenitor Cells ◽  
Comprehensive Picture ◽  
Proper Diagnosis ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy characterized by the clonal expansion of myeloid stem and progenitor cells in the bone marrow, peripheral blood, and other tissues. AML results from the acquisition of gene mutations or chromosomal abnormalities that induce proliferation or block differentiation of hematopoietic progenitors. A combination of cytogenetic profiling and gene mutation analyses are essential for the proper diagnosis, classification, prognosis, and treatment of AML. In the present review, we provide a summary of genomic abnormalities in AML that have emerged as both markers of disease and therapeutic targets. We discuss the abnormalities of RARA, FLT3, BCL2, IDH1, and IDH2, their significance as therapeutic targets in AML, and how various mechanisms cause resistance to the currently FDA-approved inhibitors. We also discuss the limitations of current genomic approaches for producing a comprehensive picture of the activated signaling pathways at diagnosis or at relapse in AML patients, and how innovative technologies combining genomic and functional methods will improve the discovery of novel therapeutic targets in AML. The ultimate goal is to optimize a personalized medicine approach for AML patients and possibly those with other types of cancers.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

scholarly journals Successful combination chemotherapy involving clofarabine, cyclophosphamide, and etoposide for pediatric relapsed acute myeloid leukemia: A case report

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110155
Author(s):  
Sachio Fujita ◽  
Ryosuke Matsuno ◽  
Naoko Kawabata ◽  
Yumiko Sugishita ◽  
Ryota Kaneko ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Gemtuzumab Ozogamicin ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Positive Effects ◽  
Refractory Acute Myeloid Leukemia ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

Limited salvage chemotherapies are available for relapsed/refractory acute myeloid leukemia. Herein, we described successful reinduction chemotherapy, involving a combination of clofarabine, cyclophosphamide, and etoposide, in a 12-year-old male with relapsed acute myeloid leukemia prior to allogeneic bone marrow transplantation from his father. Although treatment with a combination of fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin, and gemtuzumab ozogamicin had no positive effects, the aforementioned clofarabine-based chemotherapy induced complete remission and allowed the transplantation to go ahead. The abovementioned regimen may be useful for induction chemotherapy prior to hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia.

scholarly journals Nanopore Targeted Sequencing for Rapid Gene Mutations Detection in Acute Myeloid Leukemia

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1026 ◽  
Author(s):  
Cumbo ◽  
Minervini ◽  
Orsini ◽  
Anelli ◽  
Zagaria ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Cost ◽  
Gene Mutations ◽  
Predictive Biomarkers ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cebpa Mutations ◽  
Targeted Gene Sequencing ◽  
Acute Myeloid

Acute myeloid leukemia (AML) clinical settings cannot do without molecular testing to confirm or rule out predictive biomarkers for prognostic stratification, in order to initiate or withhold targeted therapy. Next generation sequencing offers the advantage of the simultaneous investigation of numerous genes, but these methods remain expensive and time consuming. In this context, we present a nanopore-based assay for rapid (24 h) sequencing of six genes (NPM1, FLT3, CEBPA, TP53, IDH1 and IDH2) that are recurrently mutated in AML. The study included 22 AML patients at diagnosis; all data were compared with the results of S5 sequencing, and discordant variants were validated by Sanger sequencing. Nanopore approach showed substantial advantages in terms of speed and low cost. Furthermore, the ability to generate long reads allows a more accurate detection of longer FLT3 internal tandem duplications and phasing double CEBPA mutations. In conclusion, we propose a cheap, rapid workflow that can potentially enable all basic molecular biology laboratories to perform detailed targeted gene sequencing analysis in AML patients, in order to define their prognosis and the appropriate treatment.

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