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Article ; Online: PharmGKB summary: acyclovir/ganciclovir pathway.

Maillard, Maud / Gong, Li / Nishii, Rina / Yang, Jun J / Whirl-Carrillo, Michelle / Klein, Teri E

2022 Volume 32, Issue 5, Page(s) 201–208

MeSH term(s)	Acyclovir/therapeutic use ; Antiviral Agents/therapeutic use ; Ganciclovir ; Humans
Chemical Substances	Antiviral Agents ; Ganciclovir (P9G3CKZ4P5) ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2022-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2175826-8
ISSN	1744-6880 ; 0960-314X ; 1744-6872
ISSN (online)	1744-6880
ISSN	0960-314X ; 1744-6872
DOI	10.1097/FPC.0000000000000474
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Article ; Online: Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Escherich, Carolin S / Chen, Wenan / Li, Yizhen / Yang, Wenjian / Nishii, Rina / Li, Zhenhua / Raetz, Elizabeth A / Devidas, Meenakshi / Wu, Gang / Nichols, Kim E / Inaba, Hiroto / Pui, Ching-Hon / Jeha, Sima / Camitta, Bruce Matthew / Larsen, Eric C / Hunger, Stephen P / Loh, Mignon L / Yang, Jun J

Blood

2024

Abstract: Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia ... ...

Abstract	Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023023336
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Article ; Online: Relative bioavailability of fedratinib through various alternative oral administration methods in healthy adults.

Chen, Yizhe / Wyatt, David / Attanasio, Massimo / Thomas, Mark / Thomas, Michael / He, Bing / Nishii, Rina / Liu, Liangang / Shan, Vivian / Xue, Yongjun / Carayannopoulos, Leonidas N / Ogasawara, Ken / Krishna, Gopal

Cancer chemotherapy and pharmacology

2023 Volume 93, Issue 4, Page(s) 307–317

Abstract: Fedratinib is an oral Janus kinase 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis; however, some patients have difficulty with oral dosing. This randomized, phase 1, open-label, 2-part crossover ... ...

Abstract	Fedratinib is an oral Janus kinase 2-selective inhibitor for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis; however, some patients have difficulty with oral dosing. This randomized, phase 1, open-label, 2-part crossover study evaluated the relative bioavailability, safety, tolerability, taste, and palatability of fedratinib resulting from various alternative oral administration methods in healthy adults. Participants could receive fedratinib 400 mg orally as intact capsules along with a nutritional supplement; as contents of capsules dispersed in a nutritional supplement, delivered via nasogastric tube; or as a divided dose of 200 mg orally twice daily as intact capsules with a nutritional supplement. Fifty-eight participants received treatment. Total exposure to fedratinib was similar after oral administration of intact capsules or when dispersed in a nutritional supplement (area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration geometric mean ratio [AUC
MeSH term(s)	Adult ; Humans ; Biological Availability ; Cross-Over Studies ; Administration, Oral ; Area Under Curve
Language	English
Publishing date	2023-11-13
Publishing country	Germany
Document type	Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-023-04612-w
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Article ; Online: Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations.

Journal of the National Cancer Institute

2024 Volume 116, Issue 5, Page(s) 702–710

Abstract: Background: Thiopurines such as mercaptopurine (MP) are widely used to treat acute lymphoblastic leukemia (ALL). Thiopurine-S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) inactivate thiopurines, and no-function variants are associated with ... ...

Abstract	Background: Thiopurines such as mercaptopurine (MP) are widely used to treat acute lymphoblastic leukemia (ALL). Thiopurine-S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) inactivate thiopurines, and no-function variants are associated with drug-induced myelosuppression. Dose adjustment of MP is strongly recommended in patients with intermediate or complete loss of activity of TPMT and NUDT15. However, the extent of dosage reduction recommended for patients with intermediate activity in both enzymes is currently not clear. Methods: MP dosages during maintenance were collected from 1768 patients with ALL in Singapore, Guatemala, India, and North America. Patients were genotyped for TPMT and NUDT15, and actionable variants defined by the Clinical Pharmacogenetics Implementation Consortium were used to classify patients as TPMT and NUDT15 normal metabolizers (TPMT/NUDT15 NM), TPMT or NUDT15 intermediate metabolizers (TPMT IM or NUDT15 IM), or TPMT and NUDT15 compound intermediate metabolizers (TPMT/NUDT15 IM/IM). In parallel, we evaluated MP toxicity, metabolism, and dose adjustment using a Tpmt/Nudt15 combined heterozygous mouse model (Tpmt+/-/Nudt15+/-). Results: Twenty-two patients (1.2%) were TPMT/NUDT15 IM/IM in the cohort, with the majority self-reported as Hispanics (68.2%, 15/22). TPMT/NUDT15 IM/IM patients tolerated a median daily MP dose of 25.7 mg/m2 (interquartile range = 19.0-31.1 mg/m2), significantly lower than TPMT IM and NUDT15 IM dosage (P < .001). Similarly, Tpmt+/-/Nudt15+/- mice displayed excessive hematopoietic toxicity and accumulated more metabolite (DNA-TG) than wild-type or single heterozygous mice, which was effectively mitigated by a genotype-guided dose titration of MP. Conclusion: We recommend more substantial dose reductions to individualize MP therapy and mitigate toxicity in TPMT/NUDT15 IM/IM patients.
MeSH term(s)	Humans ; Methyltransferases/genetics ; Methyltransferases/metabolism ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Mercaptopurine/administration & dosage ; Mercaptopurine/adverse effects ; Child ; Male ; Animals ; Female ; Mice ; Adolescent ; Antimetabolites, Antineoplastic/adverse effects ; Antimetabolites, Antineoplastic/administration & dosage ; Child, Preschool ; Genotype ; Nudix Hydrolases
Chemical Substances	NUDT15 protein, human (EC 2.6.1.-) ; Methyltransferases (EC 2.1.1.-) ; Pyrophosphatases (EC 3.6.1.-) ; Mercaptopurine (E7WED276I5) ; TPMT protein, human (EC 2.1.1.67) ; Antimetabolites, Antineoplastic ; Nudix Hydrolases (EC 3.6.1.-)
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djae004
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Article: Germline Genetic

Escherich, Carolin / Chen, Wenan / Li, Yizhen / Yang, Wenjian / Nishii, Rina / Li, Zhenhua / Raetz, Elizabeth A / Devidas, Meenakshi / Wu, Gang / Nichols, Kim E / Inaba, Hiroto / Pui, Ching-Hon / Jeha, Sima / Camitta, Bruce M / Larsen, Eric / Hunger, Stephen P / Loh, Mignon L / Yang, Jun J

Research square

2023

Abstract: Biallelic mutation in the DNA-damage repair ... ...

Abstract	Biallelic mutation in the DNA-damage repair gene
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3171814/v1
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Article ; Online: NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir.

Nishii, Rina / Mizuno, Takanori / Rehling, Daniel / Smith, Colton / Clark, Brandi L / Zhao, Xujie / Brown, Scott A / Smart, Brandon / Moriyama, Takaya / Yamada, Yuji / Ichinohe, Tatsuo / Onizuka, Makoto / Atsuta, Yoshiko / Yang, Lei / Yang, Wenjian / Thomas, Paul G / Stenmark, Pål / Kato, Motohiro / Yang, Jun J

Nature communications

2021 Volume 12, Issue 1, Page(s) 4181

Abstract: Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 ... ...

Abstract	Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
MeSH term(s)	Acyclovir/pharmacology ; Acyclovir/therapeutic use ; Adolescent ; Adult ; Aged ; Animals ; Antibiotic Prophylaxis ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Biological Variation, Population/genetics ; Cell Line ; Child ; Child, Preschool ; Crystallography, X-Ray ; Cytomegalovirus/drug effects ; Cytomegalovirus/genetics ; Cytomegalovirus/isolation & purification ; Cytomegalovirus Infections/diagnosis ; Cytomegalovirus Infections/etiology ; Cytomegalovirus Infections/prevention & control ; Cytomegalovirus Infections/virology ; DNA, Viral/blood ; DNA, Viral/isolation & purification ; Disease Models, Animal ; Drug Resistance, Viral ; Female ; Ganciclovir/analogs & derivatives ; Ganciclovir/pharmacology ; Ganciclovir/therapeutic use ; Hematopoietic Stem Cell Transplantation/adverse effects ; Host Microbial Interactions/genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Muromegalovirus/isolation & purification ; Muromegalovirus/pathogenicity ; Pharmacogenomic Variants ; Polymorphism, Single Nucleotide ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; Pyrophosphatases/ultrastructure ; Treatment Outcome ; Young Adult
Chemical Substances	Antiviral Agents ; DNA, Viral ; ganciclovir triphosphate ; NUDT15 protein, human (EC 2.6.1.-) ; Pyrophosphatases (EC 3.6.1.-) ; Ganciclovir (P9G3CKZ4P5) ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2021-07-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-24509-7
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Article ; Online: Crystal structures of NUDT15 variants enabled by a potent inhibitor reveal the structural basis for thiopurine sensitivity.

Rehling, Daniel / Zhang, Si Min / Jemth, Ann-Sofie / Koolmeister, Tobias / Throup, Adam / Wallner, Olov / Scaletti, Emma / Moriyama, Takaya / Nishii, Rina / Davies, Jonathan / Desroses, Matthieu / Rudd, Sean G / Scobie, Martin / Homan, Evert / Berglund, Ulrika Warpman / Yang, Jun J / Helleday, Thomas / Stenmark, Pål

The Journal of biological chemistry

2021 Volume 296, Page(s) 100568

Abstract: The enzyme NUDT15 efficiently hydrolyzes the active metabolites of thiopurine drugs, which are routinely used for treating cancer and inflammatory diseases. Loss-of-function variants in NUDT15 are strongly associated with thiopurine intolerance, such as ... ...

Abstract	The enzyme NUDT15 efficiently hydrolyzes the active metabolites of thiopurine drugs, which are routinely used for treating cancer and inflammatory diseases. Loss-of-function variants in NUDT15 are strongly associated with thiopurine intolerance, such as leukopenia, and preemptive NUDT15 genotyping has been clinically implemented to personalize thiopurine dosing. However, understanding the molecular consequences of these variants has been difficult, as no structural information was available for NUDT15 proteins encoded by clinically actionable pharmacogenetic variants because of their inherent instability. Recently, the small molecule NUDT15 inhibitor TH1760 has been shown to sensitize cells to thiopurines, through enhanced accumulation of 6-thio-guanine in DNA. Building upon this, we herein report the development of the potent and specific NUDT15 inhibitor, TH7755. TH7755 demonstrates a greatly improved cellular target engagement and 6-thioguanine potentiation compared with TH1760, while showing no cytotoxicity on its own. This potent inhibitor also stabilized NUDT15, enabling analysis by X-ray crystallography. We have determined high-resolution structures of the clinically relevant NUDT15 variants Arg139Cys, Arg139His, Val18Ile, and V18_V19insGlyVal. These structures provide clear insights into the structural basis for the thiopurine intolerance phenotype observed in patients carrying these pharmacogenetic variants. These findings will aid in predicting the effects of new NUDT15 sequence variations yet to be discovered in the clinic.
MeSH term(s)	Crystallography, X-Ray ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Models, Molecular ; Mutation ; Protein Conformation ; Pyrophosphatases/antagonists & inhibitors ; Pyrophosphatases/chemistry ; Pyrophosphatases/genetics ; Thioguanine/chemistry ; Thioguanine/pharmacology
Chemical Substances	Enzyme Inhibitors ; NUDT15 protein, human (EC 2.6.1.-) ; Pyrophosphatases (EC 3.6.1.-) ; Thioguanine (FTK8U1GZNX)
Language	English
Publishing date	2021-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100568
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Article ; Online: Low NUDT15 expression levels due to biallelic NUDT15 variants and 6-mercaptopurine intolerance.

British journal of haematology

2022 Volume 199, Issue 2, Page(s) 270–276

Abstract: 6-Mercaptopurine (6-MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6-MP-associated adverse effects such as ... ...

Abstract	6-Mercaptopurine (6-MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6-MP-associated adverse effects such as myelosuppression. Patients with hypomorphic NUDT15 variants accumulate excessive levels of DNA-incorporated thioguanine in white blood cells, resulting in severe myelosuppression. Although preclinical studies suggest that these variants may influence the protein stability of NUDT15, this has not been directly characterised in patients. In this study, we report the development of a series of novel monoclonal antibodies against NUDT15, using which we quantitatively assessed NUDT15 protein levels in 37 patients with acute lymphoblastic leukaemia treated with 6-MP, using sandwich enzyme-linked immunosorbent assay (ELISA). The NUDT15 genotype was highly correlated with its protein levels (p < 0.0001), with homozygous and compound heterozygous patients showing exceedingly low NUDT15 expression. There was a positive correlation between NUDT15 protein level and 6-MP tolerance (r = 0.631, p < 0.0001). In conclusion, our results point to low NUDT15 protein abundance as the biochemical basis for NUDT15-mediated 6-MP intolerance, thus providing a phenotypic readout of inherited NUDT15 deficiency.
MeSH term(s)	Child ; Humans ; Antibodies, Monoclonal/therapeutic use ; Mercaptopurine/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Pyrophosphatases/genetics ; Thioguanine/therapeutic use
Chemical Substances	Antibodies, Monoclonal ; Mercaptopurine (E7WED276I5) ; Pyrophosphatases (EC 3.6.1.-) ; Thioguanine (FTK8U1GZNX) ; NUDT15 protein, human (EC 2.6.1.-)
Language	English
Publishing date	2022-07-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18375
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Article ; Online: The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in Japanese children with acute lymphoblastic leukemia.

Moriyama, Takaya / Nishii, Rina / Lin, Ting-Nien / Kihira, Kentaro / Toyoda, Hidemi / Jacob, Nersting / Kato, Motohiro / Koh, Katsuyoshi / Inaba, Hiroto / Manabe, Atsushi / Schmiegelow, Kjeld / Yang, Jun J / Hori, Hiroki

Pharmacogenetics and genomics

2017 Volume 27, Issue 6, Page(s) 236–239

Abstract: Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major ... ...

Abstract	Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting hematopoietic toxicity. Recently, germline variants in NUDT15 have been identified as a major genetic cause for MP-related bone marrow suppression, and there is increasing interest in the clinical implementation of NUDT15 genotype-guided MP dose individualization. Therefore, we sought to evaluate the effects of NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform NUDT15 genotype-guided MP dosing. In 55 Japanese children with acute lymphoblastic leukemia, we simultaneously measured both thioguanine nucleotides (TGN) in red blood cells and DNA-incorporated thioguanine (DNA-TG) in white blood cells. TGN levels were significantly lower in patients with NUDT15 deficiency, likely because of toxicity-related MP dose reduction. In contrast, when exposed to the same dose of MP, DNA-TG accumulated more efficiently in vivo with increasing number of risk alleles in NUDT15 (P=4.0×10). Cytosolic TGN and nuclear DNA-TG were correlated positively with each other across genotype groups (P=6.5×10), but the ratio of DNA-TG to TGN was significantly higher in NUDT15-deficient patients (P=3.6×10), consistent with excessive MP activation. In conclusion, our results suggest that DNA-TG is a more relevant MP metabolite than TGN to inform NUDT15 genotype-guided dose adjustments.
MeSH term(s)	Adolescent ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Child ; Child, Preschool ; Female ; Germ-Line Mutation ; Humans ; Infant ; Japan ; Male ; Pharmacogenomic Variants ; Polymorphism, Single Nucleotide ; Precision Medicine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Purines/pharmacology ; Purines/therapeutic use ; Pyrophosphatases/genetics ; Thioguanine/blood
Chemical Substances	Antineoplastic Agents ; Purines ; NUDT15 protein, human (EC 2.6.1.-) ; Pyrophosphatases (EC 3.6.1.-) ; Thioguanine (FTK8U1GZNX)
Language	English
Publishing date	2017-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2175826-8
ISSN	1744-6880 ; 0960-314X ; 1744-6872
ISSN (online)	1744-6880
ISSN	0960-314X ; 1744-6872
DOI	10.1097/FPC.0000000000000282
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Article ; Online: An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia.

Tanaka, Yoichi / Yeoh, Allen Eng Juh / Moriyama, Takaya / Li, Chi-Kong / Kudo, Ko / Arakawa, Yuki / Buaboonnam, Jassada / Zhang, Hui / Liu, Hsi-Che / Ariffin, Hany / Chen, Zhiwei / Kham, Shirley K Y / Nishii, Rina / Hasegawa, Daisuke / Fujimura, Junya / Keino, Dai / Kondoh, Kensuke / Sato, Atsushi / Ueda, Takahiro /

Yamamoto, Masaki / Taneyama, Yuichi / Hino, Moeko / Takagi, Masatoshi / Ohara, Akira / Ito, Etsuro / Koh, Katsuyoshi / Hori, Hiroki / Manabe, Atsushi / Yang, Jun J / Kato, Motohiro

Haematologica

2021 Volume 106, Issue 7, Page(s) 2026–2029

MeSH term(s)	Alleles ; Child ; Humans ; Mercaptopurine/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Pyrophosphatases/genetics ; Retrospective Studies
Chemical Substances	Mercaptopurine (E7WED276I5) ; Pyrophosphatases (EC 3.6.1.-)
Language	English
Publishing date	2021-07-01
Publishing country	Italy
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2020.266320
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