Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Informed Consent
2.2. Measurement of Residual Plasma Imatinib Concentrations (ima[C]min)
2.3. Whole-Exome Sequencing (WES)
2.4. RNA-Sequencing
2.5. Association Studies
2.6. Linear Regression Analysis
3. Results
3.1. Patient Population
3.2. Association Analysis in Binary Mode
Phenotype Code | Phenotype | Samples (n) |
Binary mode |
| 92 |
|
3.3. Linear Regression Analysis of ima[C]min
3.4. Haplotype Analysis
3.5. Transcriptomic Changes in Patients with Plasma ima[C]min > 1000 ng/mL
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Goldman, J.M. Chronic Myeloid Leukemia: A Historical Perspective. Semin. Hematol. 2010, 47, 302–311. [Google Scholar] [CrossRef] [PubMed]
- Druker, B.J.; Talpaz, M.; Resta, D.J.; Peng, B.; Buchdunger, E.; Ford, J.M.; Lydon, N.B.; Kantarjian, H.; Capdeville, R.; Ohno-Jones, S.; et al. Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia. N. Engl. J. Med. 2001, 344, 1031–1037. [Google Scholar] [CrossRef] [PubMed]
- On behalf of the TOPS investigators; Baccarani, M.; Druker, B.J.; Branford, S.; Kim, D.-W.; Pane, F.; Mongay, L.; Mone, M.; Ortmann, C.-E.; Kantarjian, H.M.; et al. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: Final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study. Int. J. Hematol. 2014, 99, 616–624. [Google Scholar] [CrossRef] [PubMed]
- Deininger, M.W.; Kopecky, K.J.; Radich, J.P.; Kamel-Reid, S.; Stock, W.; Paietta, E.; Emanuel, P.D.; Tallman, M.; Wadleigh, M.; Larson, R.A.; et al. Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: Results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia. Br. J. Haematol. 2014, 164, 223–232. [Google Scholar] [CrossRef] [PubMed]
- Guilhot, F.; Rigal-Huguet, F.; Guilhot, J.; Guerci-Bresler, A.-P.; Maloisel, F.; Rea, D.; Coiteux, V.; Gardembas, M.; Berthou, C.; Vekhoff, A.; et al. Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: Results from the French SPIRIT phase III randomised trial. Leukemia 2021, 35, 2332–2345. [Google Scholar] [CrossRef] [PubMed]
- Hehlmann, R.; Müller, M.C.; Lauseker, M.; Hanfstein, B.; Fabarius, A.; Schreiber, A.; Proetel, U.; Pletsch, N.; Pfirrmann, M.; Haferlach, C.; et al. Deep Molecular Response Is Reached by the Majority of Patients Treated With Imatinib, Predicts Survival, and Is Achieved More Quickly by Optimized High-Dose Imatinib: Results From the Randomized CML-Study IV. J. Clin. Oncol. 2014, 32, 415–423. [Google Scholar] [CrossRef] [PubMed]
- Gafter-Gvili, A.; Leader, A.; Gurion, R.; Vidal, L.; Ram, R.; Shacham-Abulafia, A.; Ben-Bassat, I.; Lishner, M.; Shpilberg, O.; Raanani, P. High-dose imatinib for newly diagnosed chronic phase chronic myeloid leukemia patients—Systematic review and meta-analysis. Am. J. Hematol. 2011, 86, 657–662. [Google Scholar] [CrossRef]
- Liu, Y.; Fang, B.; Jiang, J.; Wang, P. Clinical efficacy and safety of high-dose imatinib for chronic myeloid leukemia patients: An updated meta-analysis. J. Can. Res. Ther. 2016, 12, 23. [Google Scholar] [CrossRef] [PubMed]
- Bouchet, S.; Titier, K.; Moore, N.; Lassalle, R.; Ambrosino, B.; Poulette, S.; Schuld, P.; Belanger, C.; Mahon, F.; Molimard, M. Therapeutic drug monitoring of imatinib in chronic myeloid leukemia: Experience from 1216 patients at a centralized laboratory. Fundam. Clin. Pharma 2013, 27, 690–697. [Google Scholar] [CrossRef]
- Larson, R.A.; Druker, B.J.; Guilhot, F.; O’Brien, S.G.; Riviere, G.J.; Krahnke, T.; Gathmann, I.; Wang, Y. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: A subanalysis of the IRIS study. Blood 2008, 111, 4022–4028. [Google Scholar] [CrossRef]
- Gotta, V.; Bouchet, S.; Widmer, N.; Schuld, P.; Decosterd, L.A.; Buclin, T.; Mahon, F.-X.; Csajka, C.; Molimard, M. Large-scale imatinib dose–concentration–effect study in CML patients under routine care conditions. Leuk. Res. 2014, 38, 764–772. [Google Scholar] [CrossRef] [PubMed]
- Johnson-Ansah, H.; Maneglier, B.; Huguet, F.; Legros, L.; Escoffre-Barbe, M.; Gardembas, M.; Cony-Makhoul, P.; Coiteux, V.; Sutton, L.; Abarah, W.; et al. Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia. Pharmaceutics 2022, 14, 1676. [Google Scholar] [CrossRef] [PubMed]
- Delord, M.; Rousselot, P.; Cayuela, J.M.; Sigaux, F.; Guilhot, J.; Preudhomme, C.; Guilhot, F.; Loiseau, P.; Raffoux, E.; Geromin, D.; et al. High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients. Oncotarget 2013, 4, 1582–1591. [Google Scholar] [CrossRef] [PubMed]
- Sailaja, K.; Rao, V.R.; Yadav, S.; Reddy, R.R.; Surekha, D.; Rao, D.N.; Raghunadharao, D.; Vishnupriya, S. Intronic SNPs of TP53 gene in chronic myeloid leukemia: Impact on drug response. J. Nat. Sci. Biol. Med. 2012, 3, 182–185. [Google Scholar] [CrossRef] [PubMed]
- Alarcón-Payer, C.; Sánchez Suárez, M.D.M.; Martín Roldán, A.; Puerta Puerta, J.M.; Jiménez Morales, A. Impact of Genetic Polymorphisms and Biomarkers on the Effectiveness and Toxicity of Treatment of Chronic Myeloid Leukemia and Acute Myeloid Leukemia. J. Pers. Med. 2022, 12, 1607. [Google Scholar] [CrossRef] [PubMed]
- Shriyan, B.; Mehta, P.; Patil, A.; Jadhav, S.; Kumar, S.; Puri, A.S.; Govalkar, R.; Krishnamurthy, M.N.; Punatar, S.; Gokarn, A.; et al. Role of ADME gene polymorphisms on imatinib disposition: Results from a population pharmacokinetic study in chronic myeloid leukaemia. Eur. J. Clin. Pharmacol. 2022, 78, 1321–1330. [Google Scholar] [CrossRef] [PubMed]
- Yin, C.-X.; Chen, W.-W.; Zhong, Q.-X.; Jiang, X.-J.; Wang, Z.-X.; Li, X.-D.; Ye, J.-Y.; Cao, R.; Liao, L.-B.; Wu, F.-Q.; et al. Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia. Exp. Ther. Med. 2016, 11, 2061–2065. [Google Scholar] [CrossRef] [PubMed]
- He, S.; Shao, Q.; Zhao, J.; Bian, J.; Zhao, Y.; Hao, X.; Li, Y.; Hu, L.; Liu, B.; He, H.; et al. Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation. Cancer Chemother. Pharmacol. 2023, 92, 399–410. [Google Scholar] [CrossRef] [PubMed]
- Harivenkatesh, N.; Kumar, L.; Bakhshi, S.; Sharma, A.; Kabra, M.; Velpandian, T.; Gogia, A.; Shastri, S.S.; Biswas, N.R.; Gupta, Y.K. Influence of MDR1 and CYP3A5 genetic polymorphisms on trough levels and therapeutic response of imatinib in newly diagnosed patients with chronic myeloid leukemia. Pharmacol. Res. 2017, 120, 138–145. [Google Scholar] [CrossRef]
- Modena, B.D.; Doroudchi, A.; Patel, P.; Sathish, V. Leveraging genomics to uncover the genetic, environmental and age-related factors leading to asthma. In Genomic and Precision Medicine; Elsevier: Amsterdam, The Netherlands, 2019; pp. 331–381. ISBN 978-0-12-801496-7. [Google Scholar]
- Alghamdi, J.; Padmanabhan, S. Fundamentals of Complex Trait Genetics and Association Studies. In Handbook of Pharmacogenomics and Stratified Medicine; Elsevier: Amsterdam, The Netherlands, 2014; pp. 235–257. ISBN 978-0-12-386882-4. [Google Scholar]
- Purcell, S.; Neale, B.; Todd-Brown, K.; Thomas, L.; Ferreira, M.A.R.; Bender, D.; Maller, J.; Sklar, P.; De Bakker, P.I.W.; Daly, M.J.; et al. PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. Am. J. Hum. Genet. 2007, 81, 559–575. [Google Scholar] [CrossRef]
- Park, J.-H.; Gail, M.H.; Weinberg, C.R.; Carroll, R.J.; Chung, C.C.; Wang, Z.; Chanock, S.J.; Fraumeni, J.F.; Chatterjee, N. Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants. Proc. Natl. Acad. Sci. USA 2011, 108, 18026–18031. [Google Scholar] [CrossRef] [PubMed]
- Barrett, J.C.; Fry, B.; Maller, J.; Daly, M.J. Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21, 263–265. [Google Scholar] [CrossRef] [PubMed]
- McLean, L.A.; Gathmann, I.; Capdeville, R.; Polymeropoulos, M.H.; Dressman, M. Pharmacogenomic Analysis of Cytogenetic Response in Chronic Myeloid Leukemia Patients Treated with Imatinib. Clin. Cancer Res. 2004, 10, 155–165. [Google Scholar] [CrossRef] [PubMed]
- Eskazan, A.E. Is measuring plasma imatinib trough levels still an appropriate way for predicting responses in patients with chronic myeloid leukemia? Leuk. Lymphoma 2019, 60, 2094–2095. [Google Scholar] [CrossRef] [PubMed]
- Löfgren, C.; Lehmann, S.; Jönsson-Videsäter, K.; Möllgård, L.; Linder, O.; Tidefelt, U.; Hassan, M.; Paul, C. Higher Plasma but not Intracellular Concentrations After Infusion With Liposomal Daunorubicin Compared With Conventional Daunorubicin in Adult Acute Myeloid Leukemia. Ther. Drug Monit. 2007, 29, 626–631. [Google Scholar] [CrossRef]
- Nagano, D.; Araki, T.; Yanagisawa, K.; Ogawa, Y.; Gohda, F.; Uchiumi, H.; Handa, H.; Nakamura, T.; Yamamoto, K. Darunavir concentration in PBMCs may be a better indicator of drug exposure in HIV patients. Eur. J. Clin. Pharmacol. 2018, 74, 1055–1060. [Google Scholar] [CrossRef]
p-Value ≤ 10−3 | p-Value ≤ 10−4 | p-Value ≤ 10−5 | p-Value ≤ 10−6 | ||||
---|---|---|---|---|---|---|---|
SNPs (n) | Genes (n) | SNPs (n) | Genes (n) | SNPs (n) | Genes (n) | SNPs (n) | Genes (n) |
845 | 479 | 130 | 76 | 24 | 11 | 4 | 1 |
SNP | SNP* | Chromosome | Gene | Minor Allele A1 | Frequent Allele A2 | Homozygote A1 (n) | Heterozygotes (n) | Homozygote A2 (n) | p-Value Linear Regression | Variant Type |
---|---|---|---|---|---|---|---|---|---|---|
rs773894 | 1 | 19 | NWD1 | G | C | 17 | 50 | 25 | 3.60 × 10−5 | intron_variant |
rs614461 | 2 | 1 | ESPNP | G | C | 2 | 41 | 49 | 6.42 × 10−5 | non_coding_transcript_exon_variant |
rs41500945 | 3 | 11 | MUC2 | T | C | 14 | 36 | 41 | 1.35 × 10−5 | intron_variant |
rs7781826 | 4 | 7 | NC_000007.14:144435107:C:A | C | A | 7 | 35 | 50 | 2.49 × 10−5 | intergenic_region |
rs56156123 | 5 | 11 | PLEKHA7 | T | C | 6 | 29 | 55 | 6.16 × 10−5 | intron_variant |
rs34933848 | 6 | 19 | SSC5D | A | G | 3 | 27 | 60 | 5.66 × 10−5 | intron_variant |
rs7895028 | 7 | 10 | NC_000010.11:100656250:T:C | C | T | 22 | 20 | 41 | 1.55 × 10−5 | intergenic_region |
rs10863292 | 8 | 1 | ESRRG | C | T | 15 | 19 | 52 | 1.40 × 10−5 | intron_variant |
rs61736520 | 9 | 2 | EXOC6B | C | T | 1 | 19 | 72 | 8.30 × 10−5 | synonymous_variant |
rs796983937 | 10 | 6 | TCP10L2 | G | C | 0 | 17 | 75 | 2.46 × 10−5 | non_coding_transcript_exon_variant |
rs112924481 | 11 | 1 | ZZZ3 | C | T | 1 | 16 | 75 | 1.39 × 10−5 | intron_variant |
rs528965019 | 12 | 14 | NC_000014.9:60397689:A:G,NC_000014.9:60397689:A:T | T | A | 1 | 15 | 76 | 4.44 × 10−5 | intergenic_region |
rs151604 | 13 | 6 | CEP43 | T | C | 2 | 14 | 75 | 7.65 × 10−6 | intergenic_region |
rs11689707 | 14 | 2 | EXOC6B | C | A | 1 | 14 | 75 | 3.01 × 10−5 | intron_variant |
rs368063 | 15 | 8 | LOC100507403 | C | G | 5 | 12 | 73 | 7.39 × 10−5 | intergenic_region |
rs1490556064 | 16 | 5 | HCN1-EMB | A | C | 0 | 12 | 70 | 6.05 × 10−5 | intergenic_region |
rs7170580 | 17 | 15 | NC_000015.10:44784456:G:C,NC_000015.10:44784456:G:T | C | G | 0 | 12 | 80 | 8.92 × 10−5 | intergenic_region |
rs17588988 | 18 | 15 | TRIM69 | G | A | 0 | 11 | 81 | 5.18 × 10−5 | missense_variant |
rs16876504 | 19 | 8 | LEPROTL1 | G | A | 1 | 10 | 77 | 8.38 × 10−5 | intron_variant |
rs17229438 | 20 | 15 | MIR10393 | A | G | 0 | 10 | 82 | 2.13 × 10−5 | upstream_gene_variant |
rs55806342 | 21 | 10 | PRKG1 | A | G | 1 | 10 | 81 | 6.79 × 10−6 | synonymous_variant |
rs116049705 | 22 | 1 | AK5 | A | G | 0 | 10 | 82 | 3.78 × 10−5 | 5_prime_UTR_variant |
rs1173882568 | 23 | 7 | BPGM | T | C | 0 | 10 | 81 | 7.76 × 10−5 | intron_variant |
rs1396579274 | 24 | 7 | BPGM | T | G | 0 | 10 | 80 | 7.97 × 10−5 | intron_variant |
rs62059984 | 25 | 17 | NC_000017.11:14641601:G:A | A | G | 1 | 9 | 82 | 1.43 × 10−5 | intergenic_region |
rs79981660 | 26 | 11 | YAP1 | A | G | 1 | 9 | 82 | 2.66 × 10−5 | intron_variant |
rs142214363 | 27 | 3 | IGSF10 | G | A | 0 | 9 | 83 | 5.28 × 10−5 | synonymous_variant |
rs79390594 | 28 | 16 | ABAT | G | A | 1 | 8 | 83 | 9.65 × 10−5 | intron_variant |
rs3748271 | 29 | 12 | TCTN2 | G | A | 0 | 8 | 84 | 7.10 × 10−5 | intron_variant |
rs11057329 | 30 | 12 | TCTN2 | T | A | 0 | 8 | 84 | 7.10 × 10−5 | intron_variant |
rs10846543 | 31 | 12 | TCTN2 | G | A | 0 | 8 | 84 | 7.10 × 10−5 | intron_variant |
rs10773019 | 32 | 12 | DDX55 | G | A | 0 | 8 | 84 | 7.10 × 10−5 | missense_variant |
rs3704 | 33 | 12 | EIF2B1 | T | G | 0 | 8 | 84 | 7.10 × 10−5 | intron_variant |
rs978263 | 34 | 17 | CBX1 | A | G | 4 | 7 | 70 | 2.02 × 10−5 | upstream_gene_variant |
rs12694421 | 35 | 2 | DIRC3 | T | A | 1 | 7 | 71 | 1.55 × 10−5 | intron_variant |
rs10773020 | 36 | 12 | GTF2H3 | G | T | 1 | 7 | 84 | 8.34 × 10−5 | upstream_gene_variant |
rs6662789 | 37 | 1 | IL12RB2 | A | G | 1 | 7 | 82 | 4.13 × 10−5 | intron_variant |
rs969477092 | 38 | 5 | NIPBL | T | C | 0 | 7 | 85 | 2.04 × 10−7 | intron_variant |
rs775871417 | 39 | 5 | NIPBL | T | A | 0 | 7 | 85 | 2.04 × 10−7 | intron_variant |
rs1170486575 | 40 | 5 | NIPBL | T | G | 0 | 7 | 85 | 2.04 × 10−7 | intron_variant |
rs1346918408 | 41 | 16 | NC_000016.10:33337669:T:C | C | T | 0 | 7 | 83 | 3.24 × 10−5 | intergenic_region |
rs16845711 | 42 | 2 | STK17B | G | A | 1 | 6 | 85 | 7.62 × 10−5 | splice_region_variant&intron_variant |
rs16841010 | 43 | 2 | DNAH7 | T | C | 1 | 6 | 85 | 7.62 × 10−5 | intron_variant |
rs35767836 | 44 | 5 | EGFLAM | C | G | 0 | 6 | 86 | 4.99 × 10−6 | missense_variant |
rs41269273 | 45 | 6 | H4C12 | T | A | 0 | 6 | 86 | 6.32 × 10−5 | synonymous_variant |
rs78352502 | 46 | 14 | RPL10L | T | C | 0 | 6 | 86 | 6.88 × 10−5 | upstream_gene_variant |
chr9:27454985 | 47 | 9 | MOB3B | T | A | 0 | 6 | 85 | 2.08 × 10−5 | intron_variant |
rs45611038 | 48 | 10 | PRKCQ | A | G | 0 | 6 | 86 | 4.41 × 10−5 | intron_variant |
rs35840993 | 49 | 19 | CYP4F3 | G | A | 0 | 6 | 86 | 6.91 × 10−5 | 3_prime_UTR_variant |
rs2178045 | 50 | 7 | AUTS2 | A | G | 3 | 5 | 75 | 3.37 × 10−6 | intron_variant |
Block | Haplotype | Freq. | ima[C]min > 1000 ng/mL Ratio Counts | ima[C]min < 1000 ng/mL Ratio Counts | ima[C]min > 1000 ng/mL Frequencies | ima[C]min < 1000 ng/mL Frequencies | Chi Square | p-Value |
---|---|---|---|---|---|---|---|---|
Block 1 | AAGGA | 0.777 | 55.0:15.0 | 88.0:26.0 | 0.786 | 0.772 | 0.048 | 8.27 × 10−1 |
TTTTT | 0.190 | 12.0:58.0 | 23.0:91.0 | 0.171 | 0.202 | 0.259 | 6.11 × 10−1 | |
Block 2 | AGAACC | 0.995 | 70.0:0.0 | 111.0:1.0 | 1.000 | 0.991 | 0.628 | 4.28 × 10−1 |
Block 3 | AGGG | 0.957 | 66.0:4.0 | 110.0:4.0 | 0.943 | 0.965 | 0.507 | 4.76 × 10−1 |
TTTT | 0.043 | 4.0:66.0 | 4.0:110.0 | 0.057 | 0.035 | 0.507 | 4.76 × 10−1 | |
Block 4 | ACA | 0.880 | 62.9:7.1 | 98.9:15.1 | 0.899 | 0.868 | 0.403 | 5.25 × 10−1 |
TTT | 0.060 | 3.0:67.0 | 8.0:106.0 | 0.043 | 0.070 | 0.575 | 4.48 × 10−1 | |
ATA | 0.028 | 2.0:68.0 | 3.0:111.0 | 0.029 | 0.027 | 0.01 | 9.19 × 10−1 | |
TCA | 0.017 | 1.1:68.9 | 2.1:111.9 | 0.015 | 0.018 | 0.024 | 8.77 × 10−1 | |
TTA | 0.010 | 1.0:69.0 | 1.0:113.0 | 0.014 | 0.008 | 0.117 | 7.33 × 10−1 | |
Block 5 | CAGAAC | 0.962 | 63.0:7.0 | 114.0:0.0 | 0.900 | 1.000 | 11.851 | 6.00 × 10−4 |
TTTAAC | 0.011 | 2.0:68.0 | 0.0:114.0 | 0.029 | 0.000 | 3.293 | 6.96 × 10−2 | |
TTTTAC | 0.011 | 2.0:68.0 | 0.0:114.0 | 0.029 | 0.000 | 3.293 | 6.96 × 10−2 | |
TTTTTT | 0.011 | 2.0:68.0 | 0.0:114.0 | 0.029 | 0.000 | 3.293 | 6.96 × 10−2 | |
Block 6 | AAAA | 0.886 | 62.0:8.0 | 101.0:13.0 | 0.886 | 0.886 | 0.000 | 9.96 × 10−1 |
TTTA | 0.076 | 5.0:65.0 | 9.0:105.0 | 0.071 | 0.079 | 0.035 | 8.52 × 10−1 | |
TTTT | 0.022 | 2.0:68.0 | 2.0:112.0 | 0.029 | 0.018 | 0.248 | 6.19 × 10−1 | |
Block 7 | CAACAAA | 0.989 | 69.0:1.0 | 113.0:1.0 | 0.986 | 0.991 | 0.123 | 7.26 × 10−1 |
TTTTTTT | 0.011 | 1.0:69.0 | 1.0:113.0 | 0.014 | 0.009 | 0.123 | 7.26 × 10−1 |
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Bruzzoni-Giovanelli, H.; Zouali, H.; Sahbatou, M.; Maneglier, B.; Cayuela, J.-M.; Rebollo, A.; Marin, G.H.; Geromin, D.; Tomczak, C.; Alberdi, A.; et al. Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients. Pharmaceutics 2024, 16, 834. https://doi.org/10.3390/pharmaceutics16060834
Bruzzoni-Giovanelli H, Zouali H, Sahbatou M, Maneglier B, Cayuela J-M, Rebollo A, Marin GH, Geromin D, Tomczak C, Alberdi A, et al. Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients. Pharmaceutics. 2024; 16(6):834. https://doi.org/10.3390/pharmaceutics16060834
Chicago/Turabian StyleBruzzoni-Giovanelli, Heriberto, Habib Zouali, Mourad Sahbatou, Benjamin Maneglier, Jean-Michel Cayuela, Angelita Rebollo, Gustavo H. Marin, Daniela Geromin, Carole Tomczak, Antonio Alberdi, and et al. 2024. "Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients" Pharmaceutics 16, no. 6: 834. https://doi.org/10.3390/pharmaceutics16060834
APA StyleBruzzoni-Giovanelli, H., Zouali, H., Sahbatou, M., Maneglier, B., Cayuela, J.-M., Rebollo, A., Marin, G. H., Geromin, D., Tomczak, C., Alberdi, A., Deleuze, J.-F., & Rousselot, P. (2024). Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients. Pharmaceutics, 16(6), 834. https://doi.org/10.3390/pharmaceutics16060834