scholarly journals Prognostic Significance of TP53 Mutations and Single Nucleotide Polymorphisms in Acute Myeloid Leukemia: A case Series and Literature Review

2014 ◽  
Vol 15 (4) ◽  
pp. 1603-1609 ◽  
Author(s):  
Simon Blechman Zeichner ◽  
Sarah Alghamdi ◽  
Gina Elhammady ◽  
Robert John Poppiti ◽  
Amilcar Castellano-Sanchez
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Literature Review ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Case Series ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tp53 Mutations ◽  
Acute Myeloid

IL-17 A and IL-17 F single nucleotide polymorphisms and acute myeloid leukemia susceptibility and response to induction therapy in Egypt

Meta Gene ◽  
2020 ◽  
Vol 26 ◽  
pp. 100773
Author(s):  
Rania A. Zayed ◽  
Zainab El-Saadany ◽  
Hanan Nour Raslan ◽  
Mohammed Ghareeb ◽  
Dalia Ibraheem ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Acute Myeloid

Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia

2020 ◽  
pp. 1-10
Author(s):  
Juan Eduardo Megías-Vericat ◽  
David Martínez-Cuadrón ◽  
María José Herrero ◽  
Rebeca Rodríguez-Veiga ◽  
Antonio Solana-Altabella ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Acute Myeloid

Influence of Single Nucleotide Polymorphisms in Anthracycline Metabolism Pathway in Standard Induction of Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4845-4845
Author(s):  
Juan Eduardo Megías ◽  
Pau Montesinos ◽  
María José Herrero ◽  
Federico Moscardó ◽  
Virginia Bosó ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Nucleotide Polymorphisms ◽  
Myeloid Leukemia ◽  
Skin Toxicity ◽  
Hematologic Toxicity ◽  
Prognostic Impact ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
The Impact ◽  
Acute Myeloid

Abstract Background: Single nucleotide polymorphisms (SNPs) within the genes involving drug detoxification enzymes of anthracyclines could lead to interindividual differences in treatment outcome. Several studies suggested, in different kinds of cancer, that SNPs of genes coding anthracyclines metabolism may influence their effectiveness or toxicity, being well-known their association with cardiotoxicity. The impact of these polymorphisms in adult acute myeloid leukemia (AML) patients treated with the combination of cytarabine and anthracyclines for induction remains undetermined. Methods: SNPs of anthracycline metabolism genes previously associated with clinical significance in other malignances (CBR3:rs1056892, rs8133052, NQO1 rs1800566, NQO2 rs1143684, NOS3:rs1799983, rs2070744, MnSOD rs4880) were evaluated in 225 adult patients at initial diagnosis from AML using a Sequenom (iPLEX) mass spectrometry-based multiplex genotyping assay (Sequenom, San Diego, CA). All patients received induction chemotherapy consisting of idarubicin plus cytarabine (PETHEMA-LMA 99, 2007 and 2010 trials). Efficacy of first induction cycle was evaluated comparing complete remission (CR) vs. partial remission or resistance. Patients dying during induction were considered as no evaluable for efficacy. Based on WHO grading scale, toxicities were grouped as binary variables (grade 0-1 vs. grade 2-4). The grade of toxicity assigned to an organ group was the maximum grade of all the specific toxicities within that group. Hematologic toxicity was measured with the time to neutropenia and thrombocytopenia recovery since first day of chemotherapy. Genotypes were studied with co-dominant model. Association between variables was assessed using linear and logistic regression adjusting for age, gender, ECOG, leukocyte and platelet count at diagnosis (R® version 3.1.2). Results: The median age of patients was 51.1 years (16-78 years). There were no statistically significant differences in CR. Nevertheless, several associations were obtained between NQO1, NQO2, NOS3 and MnSOD polymorphisms and toxicities (significant toxicities were summarized in table 1 and 2). Table 1. Significant association between SNPs in gene metabolizers and different toxicities Toxicity Gene/SNP Genotypes Grade 0-1 n (%) Grade 2-4 n (%) OR (95%IC) P Cardiotoxicity NQO2 rs1143684 TT TC 119 (86.2) 74 (94.9) 19 (13.8) 4 (5.1) 0.26 (0.07-0.77) 0.025 Neurotoxicity NOS3 rs1799983 GG GT 71 (84.5) 101 (94.4) 13 (15.5) 6 (5.6) 0.28 (0.09-0.80) 0.022 Skin toxicity NOS3 rs1799983 GG GT TT 45 (53.6) 78 (72.9) 26 (76.5) 39 (46.4) 29 (27.1) 8 (23.5) 0.44 (0.24-0.82) 0.36 (0.14-0.88) 0.010 0.030 Skin toxicity NQO1 rs1800566 CC CT 78 (60.9) 64 (74.4) 50 (39.1) 29 (25.6) 0.53 (0.28-0.97) 0.042 Skin toxicity NQO2 rs1143684 TT CC 5.49 (1.19-38.9) 0.044 Gastrointestinal toxicity NQO2 rs1143684 TT CC 91 (65.9) 2 (25.0) 47 (34.1) 6 (75.0) 5.5 (1.19-38.99) 0.043 Mucositis NQO1 rs1800566 CC TT 119 (93.0) 8 (72.7) 9 (7.0) 3 (27.3) 6.1 (1.03-33.1) 0.035 Mucositis NQO2 rs1143684 TT CC 128 (92.8) 5 (62.5) 10 (7.2) 3 (37.5) 8.8 (1.53-45.60) 0.010 Nephrotoxicity MnSOD rs4880 TT CC 47 (81.0) 55 (94.8) 11 (19.0) 3 (5.2) 0.23 (0.05-0.86) 0.042 Nephrotoxicity NQO1 rs1800566 CC TT 114 (89.1) 8 (72.7) 14 (10.9) 3 (27.3) 6.66 (1.07-38.35) 0.033 Hepatotoxicity grades 3-4 NOS3 rs2070744 CC CT 19 (24.8) 100 (67.1) 20 (51.3) 49 (32.9) 0.44 (0.20-0.94) 0.035 Table 2. Significant association between SNPs in gene metabolizers and hematologic toxicities Hematologic toxicity Gene/SNP Genotypes Mean days Logarithm of the difference (95%IC) P Time to neutropenia recovery NOS3 rs2070744 CC TT 32.7 26.7 -0.17 (-0.35 to -0.01) 0.048 Time to thrombocytopenia recovery NOS3 rs1799983 GG GT TT 35.6 28.8 30.3 -0.17 (-0.17 to -0.06) -0.15 (-0.28 to -0.01) 0.002 0.034 Conclusions: This study reveals that, as in other cancers, there is a prognostic impact of anthracycline metabolism gene polymorphisms in adult AML patients. Further studies with larger population are needed to validate these associations, which could be useful biomarkers in clinical practice. Disclosures No relevant conflicts of interest to declare.

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