The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
IntroductionPolymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1334846/full |
| _version_ | 1797258590112710656 |
|---|---|
| author | Muhammad Muhammad Muhammad Muhammad Maher Saifo Maher Saifo Majd Aljamali Majd Aljamali Mousa Alali Khaled M. Ghanem |
| author_facet | Muhammad Muhammad Muhammad Muhammad Maher Saifo Maher Saifo Majd Aljamali Majd Aljamali Mousa Alali Khaled M. Ghanem |
| author_sort | Muhammad Muhammad |
| collection | DOAJ |
| description | IntroductionPolymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).MethodsThis is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.ResultsA total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity.ConclusionApproximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL. |
| first_indexed | 2024-04-24T22:55:57Z |
| format | Article |
| id | doaj.art-5f79fb77ffb04e4aac846e4dfb5f426c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T22:55:57Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5f79fb77ffb04e4aac846e4dfb5f426c2024-03-18T04:57:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-03-011410.3389/fonc.2024.13348461334846The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemiaMuhammad Muhammad0Muhammad Muhammad1Maher Saifo2Maher Saifo3Majd Aljamali4Majd Aljamali5Mousa Alali6Khaled M. Ghanem7BASMA Pediatric Oncology Unit, Damascus, SyriaDepartment of Oncology, Albairouni University Hospital, Faculty of Medicine, Damascus University, Damascus, SyriaDepartment of Oncology, Albairouni University Hospital, Faculty of Medicine, Damascus University, Damascus, SyriaFaculty of Medicine, Damascus University, Damascus, SyriaDepartment of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Damascus, SyriaNational Commission for Biotechnology (NCBT), Damascus, SyriaDepartment of Oncology, Albairouni University Hospital, Faculty of Medicine, Damascus University, Damascus, SyriaBASMA Pediatric Oncology Unit, Damascus, SyriaIntroductionPolymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).MethodsThis is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.ResultsA total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity.ConclusionApproximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.https://www.frontiersin.org/articles/10.3389/fonc.2024.1334846/fullNUDT15genotypeacute lymphoblastic leukemiamercaptopurinetoxicitySyria |
| spellingShingle | Muhammad Muhammad Muhammad Muhammad Maher Saifo Maher Saifo Majd Aljamali Majd Aljamali Mousa Alali Khaled M. Ghanem The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia Frontiers in Oncology NUDT15 genotype acute lymphoblastic leukemia mercaptopurine toxicity Syria |
| title | The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia |
| title_full | The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia |
| title_fullStr | The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia |
| title_full_unstemmed | The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia |
| title_short | The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia |
| title_sort | frequency of nudt15 rs116855232 and its impact on mercaptopurine induced toxicity in syrian children with acute lymphoblastic leukemia |
| topic | NUDT15 genotype acute lymphoblastic leukemia mercaptopurine toxicity Syria |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1334846/full |
| work_keys_str_mv | AT muhammadmuhammad thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT muhammadmuhammad thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mahersaifo thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mahersaifo thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT majdaljamali thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT majdaljamali thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mousaalali thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT khaledmghanem thefrequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT muhammadmuhammad frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT muhammadmuhammad frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mahersaifo frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mahersaifo frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT majdaljamali frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT majdaljamali frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT mousaalali frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia AT khaledmghanem frequencyofnudt15rs116855232anditsimpactonmercaptopurineinducedtoxicityinsyrianchildrenwithacutelymphoblasticleukemia |