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Table. 4. Table 4

Previous studies on DNA-TG levels in ALL patients

Reference	Studied region	Study subjects (N)	DNA-TG (fmol/μg DNA)	RBC-TGN*	Relationship between DNA-TG and RBC-TGN	Genotypes
Warren, et al., 1995 [14]	Norway	9^†	Range 95–700	NA	NA	NA
Jacobsen, et al., 2012 [7]	Denmark	18	Median 377 (range 45–1,190)	Exact level NA	Correlated (R² = 0.78)	NA
Nielsen, et al., 2016 [15]	Denmark	50	Standard-risk patients: median 469 (range 292–891)	Standard risk patients: median 187 (range 114–508) nmol/mmol Hgb	Positively associated using linear mixed model estimate 1.22 (95% CI, 1.17–1.28, P < 0.0001)	TPMT genotypes
			Intermediate-risk pati ents: median 435 (range 238–774)	Intermediate risk patients: 217 (range 127–682) nmol/mmol Hgb
			High-risk patients: median 203 (range 107–389)	High-risk patients: median 267 (range 187–277) nmol/mmol Hgb
Nielsen, et al., 2017 [16]	European countries	750	In maintenance phase 1: median 326 (IQR 229–457; range 23–1,591)	Exact level NA	Positively associated using multiple linear mixed effect model estimate 1.227 (95% CI 1.175–1.281, P < 0.0001) in exploratory cohort (N = 42) and 1.137 (95% CI 1.118–1.155, P < 0.0001) in validation cohort (N = 304)	TPMT genotypes
Nielsen, et al., 2017 [16]	European countries	750	In maintenance phase 2: median 509 (IQR 391–666; range 44–1,559)	Exact level NA		TPMT genotypes
Moriyama, et al., 2016 [5]^‡	Japan	32	Normal NUDT15 diplotypes: 9.6 ± 4.1	NA	NA	Both NUDT15 and TPMT genotypes
			Children with one NUDT15 variant allele: 12.3 ± 4.5
			One child with two NUDT15 variant alleles: 32.4
	Singapore	32	Normal NUDT15 diplotypes: 6.0 ± 2.7	NA	NA
			Children with one NUDT15 variant allele: 8.8 ± 5.3
			Children with two NUDT15 variant alleles: 19.6 ± 6.3
Moriyama, et al., 2017 [4]	Japan	55	Mean 442.8 (range 78.1–1,054.0)	Mean 134.1 (range, 0.46–315.5 pmol/4 × 10⁸ RBCs)	Correlated using Spearman rank test (R² = 0.16, P = 0.0007)	NUDT15 genotypes (only common TPMT risk variants were analyzed, but no patients with TPMT risk variants were included)
This study	South Korea	54	Median 106.0 (range < 10.0–407.8)	Median 238.1 (range < 10.0–672.5 pmol/8 × 10⁸ RBCs)	Correlated using Spearman rank test (R = 0.68, P < 0.0001)	Both NUDT15 and TPMT genotypes (by direct sequencing to identify all variants)
			Normal NUDT15 diplotypes: 111.3 (IQR 79.1–156.4; range < 10.0–407.5)
			Children with one NUDT15 variant allele: 83.8 (IQR 38.6–134.4; range < 10.0–407.8)

*RBC-TGN levels were differently expressed using different units in previous studies; ^†Ages of study subjects were not reported. Study subjects in the other studies were pediatric ALL patients. ^‡Mean (±SD) DNA-TG level was expressed as fmol/μg DNA/mg mercaptopurine.

Abbreviations: ALL, acute lymphoblastic leukemia; 6-MP, mercaptopurine; CI, confidence interval; DNA-TG, DNA-incorporated 6-thioguanine; Hgb, hemoglobin; IQR, interquartile range; NA, not available; TPMT, thiopurine S-methyltransferase; RBC, red blood cell; RBC-TGN, 6-thioguanine nucleotide in erythrocytes.

Ann Lab Med 2021;41:145~154 https://doi.org/10.3343/alm.2021.41.2.145