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. 2022 Apr 17;14(4):878. doi: 10.3390/pharmaceutics14040878

Table 2.

Characteristics of the studies included in the systematic review for polymorphisms of the ABC transporter family.

SNP Study n Age (Range) Ethnia (Country) HWE LMA Status (%) Chemotherapy Scheme Clinical Outcomes
ABCB1
C3435T
rs1045642		 Illmer et al., 2002 [51] 405 53
(17–78)		 Caucasian
(Germany)		 Yes De novo Ara C+ MIT + ETOP + AMSA
  • -

    CR: no influence.

  • -

    OS and DFS at 4 years (TX censured): CC ↓OS (CC vs. CT p < 0.01, CC vs. CT/TT p: 0.05).

  • -

    Haplotype with G2677T/A and C1236T: wild-type ↓OS and DFS at 4 years.

  • -

    mRNA expression: CC ↓expression (p < 0.05)
Kaya et al., 2005 [52] 28 36
(20–64)		 Arabs
(Turkey)		 NR NR Ara C + ANT
  • -

    Drug sensitive/resistant: no differences (mixed with ALL cohort)
Kim DH et al., 2006 [53] 81 39
(15–72)		 Asian
(South Korea)		 Yes De novo Ara C + IDA
  • -

    CR: CC ↑CR (p: 0.05)

  • -

    OS at 3 years (TX censured): no influence.

  • -

    EFS at 3 years (TX censured): CC ↑EFS (p: 0.01)

  • -

    Haplotype with G2677T/A: wild-type ↑CR and EFS at 3 years.

  • -

    mRNA expression: CC ↓expression (p: 0.03)
Van der Holt et al., 2006 [54] 1 150 (130) 67
(60–85)		 Caucasian
(Netherlands)		 No De novo: 79Secondary: 21 Ara C + DAUNO
  • -

    CR, OS, EFS, DFS at 5 years: no influence.

  • -

    Expression and activity of P-gp: no influence
Hur et al., 2008 [55] 200 44 (NR) Asian
(South Korea)		 Yes De novo Ara C + ANT
  • -

    CR, OS, RFS and EFS at 5 years: no influence
Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian
(86%) Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
Green et al., 2012 [57] 100 63
(20–85)		 Caucasian
(Europe)		 Yes De novo (normal karyotype) Ara C + ANT or MIT +/or Others
  • -

    OS at 4 years (TX censured): no influence
Scheiner et al., 2012 [58] 2 109 (44) 34
(<1–86)		 Others: White (69.7%)
Non-white (30.3%)		 No De novo: 72.5Secondary: 18.3 Ara C + IDA
  • -

    OS at 5 years: no influence.

  • -

    EFS at 5 years: CT ↑EFS (p: 0.001)

  • -

    Expression and activity of P-gp: no influence
Falk et al., 2014 [59] 3 201 59
(18–85)		 Caucasian
(Sweden)		 Yes De novo (normal karyotype) Ara C + DAUNO or IDA ± ETOP +/or Others
  • -

    CR, OS, EFS: no influence (similar results in FLT3 wild-type subgroup).
He et al., 2014 [60] 215 43.6
(14–57)		 Asian
(China)		 Yes De novo Ara C (high doses)
  • -

    Toxicity: CC ↑acute nausea and vomiting grades 3/4 (p: 0.035, 0.010). In multivariable CC was a risk factor of vomiting (p: 0.016).

  • -

    Haplotype with ABCB1 G2677T/A (rs2032582) CC/GG ↑acute nausea and vomiting grades ¾ (0.003; 0.026) and multivariable (0.003; 0.039)
He et al., 2015 [61] 263 45.4
(14–58)		 Asian
(China)		 Yes De novo (intermediate cytogenetic risk) Ara C + DAUNO ± MIT
  • -

    OS, RFS: TT ↑OS (p: 0.004), ↑RFS (p: 0.019)

  • -

    Haplotype with G2677T/A and C1236T: TTT ↑OS (p < 0.001), ↑RFS (p: 0.005), both maintained in multivariable analysis (p: 0.001 and 0.009).

  • -

    mRNA expression: TTT haplotype ↓mRNA expression than other genotypes (p: 0.004)
Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: TT genotype ↑renal toxicity (p: 0.008)

  • -

    Haplotype C3435T, G2677T/A and C1236T: TTT ↑induction death (p: 0.020), ↑renal (p: 0.016) and hepatic (p < 0.001) toxicities.
Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: in GO arm CT/TT trend to ↑OS at 5 years (p: 0.068)

  • -

    EFS: in GO arm CT/TT↑EFS at 5 years (p: 0.022)

  • -

    DFS: in GO arm CT/TT↑DFS at 5 years (p: 0.044)

  • -

    RR: in GO arm CT/TT ↓RR at 5 years (p: 0.007)

* These results were observed especially at standard risk group
Short et al., 2020 [64] 104 68
(24–88)		 Caucasian (86%)
Black (13%)		 NR AML 82De novo: 43.9Secondary: 56.1 GO + DAC
  • -

    CR, ORR, CIR, OS, RFS: no influence
G2677T/A
rs2032582		 Van den Heuvel et al., 2001 [65] 30 34.6
(1–67)		 Caucasian
(Netherlands)		 NR Relapsed: 100 Ara C + ANT + Others
  • -

    OS after relapse at 3 years: GT ↑OS (p: 0.02)

  • -

    RFS after relapse at 3 years: GT ↑RFS (p: 0.002)
Illmer et al., 2002 [51] 405 53
(17–78)		 Caucasian
(Germany)		 Yes De novo Ara C+ MIT + ETOP + AMSA
  • -

    CR: no influence.

  • -

    OS and DFS at 4 years (TX censured): no influence.

  • -

    Haplotype with C3435T and C1236T: wild-type ↓OS and DFS at 4 years.

  • -

    mRNA expression: GG ↓expression (p: 0.05)
Kaya et al., 2005 [52] 28 36
(20–64)		 Arabs
(Turkey)		 NR NR Ara C + ANT
  • -

    Drug sensitive/resistant: no differences (mixed with ALL)
Kim DH et al., 2006 [53] 81 39
(15–72)		 Asian
(South Korea)		 Yes De novo Ara C + IDA
  • -

    CR: GG ↑CR (p: 0.04)

  • -

    OS and EFS at 3 years (TX censured): no influence.

  • -

    Haplotype with C3435T: wild-type ↑CR and EFS at 3 years.

  • -

    mRNA expression: no influence.
Van der Holt et al., 2006 [54] 1 150 (142) 67
(60–85)		 Caucasian
(Netherlands)		 Yes De novo: 79Secondary: 21 Ara C + DAUNO
  • -

    CR, OS, EFS, DFS at 5 years: no influence.

  • -

    Expression and activity of P-gp: no influence
Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
Kim YK et al., 2010 [66] 94 38
(17–79)		 Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA +BH-AC
  • -

    CR, OS: no influence

  • -

    RR: GG ↑RR (p: 0.031)

  • -

    RFS: GG ↑RFS (p: 0.005)
Green et al., 2012 [57] 100 63
(20–85)		 Caucasian
(Europe)		 Yes De novo (normal karyotype) Ara C + ANT or MIT +/or Others
  • -

    OS at 4 years(TX censured): GG ↓OS (p: 0.02)
Falk et al., 2014 [59] 3 201 59
(18–85)		 Caucasian
(Sweden)		 Yes De novo (normal karyotype) Ara C + DAUNO or IDA ± ETOP +/or Others
  • -

    CR, OS, EFS: no influence

  • -

    FLT3 wild-type subgroup: GG ↑OS (p: 0.039) against GT/TT genotypes.
He et al., 2014 [60] 215 43.6
(14–57)		 Asian
(China)		 Yes De novo Ara C (high doses)
  • -

    Toxicity: CC ↑acute nausea and vomiting grades 3/4 (p: 0.041, 0.038). Both lost in multivariable analyses.

  • -

    Haplotype with ABCB1 G2677T/A (rs1045642) CC/GG ↑acute nausea and vomiting grades ¾ (0.003; 0.026) and multivariable (0.003; 0.039)
He et al., 2015 [61] 263 45.4
(14–58)		 Asian
(China)		 Yes De novo (intermediate cytogenetic risk) Ara C + DAUNO ± MIT
  • -

    OS, RFS: TT ↑OS (p: 0.017), ↑RFS (p: 0.033)

  • -

    Haplotype with C3435T and C1236T: TTT ↑OS (p < 0.001), ↑RFS (p: 0.005), both maintained in multivariable analysis (p: 0.001 and 0.009)

  • -

    mRNA expression: TTT haplotype ↓mRNA expression than other genotypes (p: 0.004)
Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: TT genotype ↑renal (p: 0.001), hepatic (p: 0.049) toxicities & ↑time to neutropenia recovery (p: 0.047)

  • -

    Haplotype C3435T, G2677T/A and C1236T: TTT ↑induction death (p: 0.020), ↑renal (p: 0.016) and hepatic (p < 0.001) toxicities.
Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: in GO arm GT/TT↑EFS at 5 years (p: 0.016)

  • -

    DFS: in GO arm GT/TT ↑DFS at 5 years (p: 0.048)

  • -

    RR: in GO arm GT/TT ↓RR at 5 years (p: 0.001)
C1236T
rs1128503		 Illmer et al., 2002 [51] 405 53
(17–78)		 Caucasian
(Germany)		 Yes De novo Ara C+ MIT + ETOP + AMSA
  • -

    CR: no influence.

  • -

    OS and DFS at 4 years (TX censured): no influence.

  • -

    Haplotype with C3435T and G2677T/A: wild-type ↓OS and DFS at 4 years.

  • -

    mRNA expression: no influence.
Van der Holt et al., 2006 [54] 1 150 (115) 67
(60–85)		 Caucasian
(Netherlands)		 Yes De novo: 79Secondary: 21 Ara C + DAUNO
  • -

    CR, OS, EFS, DFS at 5 years: no influence.

  • -

    Expression and activity of P-gp: no influence
Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
Kim YK et al., 2010 [66] 94 38
(17–79)		 Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA +BH-AC
  • -

    CR, RR, OS and RFS: no influence
Green et al., 2012 [57] 100 63
(20–85)		 Caucasian
(Europe)		 Yes De novo (normal karyotype) Ara C + ANT or MIT +/or Others
  • -

    OS at 4 years(TX censured): CC ↓OS (p: 0.03)
Scheiner et al., 2012 [58] 2 109(44) 34
(<1–86)		 Others: White (69.7%)
Non-white (30,3%)		 Yes De novo: 72.5Secondary: 18.3 Ara C + IDA
  • -

    OS at 5 years: CC ↑OS (p: 0.04)

  • -

    EFS at 5 years: CC ↑EFS (p: 0.007)

  • -

    Expression and activity of P-gp: no influence
Falk et al., 2014 [59] 3 201 59
(18–85)		 Caucasian
(Sweden)		 Yes De novo (normal karyotype) Ara C + DAUNO or IDA ± ETOP +/or Others
  • -

    CR, OS, EFS: no influence

  • -

    FLT3 wild-type subgroup: CC ↑OS (p: 0.017) against CT/TT genotypes.
He et al., 2014 [60] 215 43.6
(14–57)		 Asian
(China)		 No De novo Ara C (high doses)
  • -

    Toxicity: not analyzed (excluded by HWE)
He et al., 2015 [61] 263 45.4
(14–58)		 Asian
(China)		 Yes De novo (intermediate cytogenetic risk) Ara C + DAUNO ± MIT
  • -

    OS, RFS: TT ↑OS (p: 0.002), ↑RFS (p: 0.001)

  • -

    Haplotype with C3435T and G2677T/A: TTT ↑OS (p < 0.001), ↑RFS (p: 0.005), both maintained in multivariable analysis (p: 0.001 and 0.009)

  • -

    mRNA expression: TTT haplotype ↓mRNA expression than other genotypes (p: 0.004)
Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: TT genotype ↑renal (p: 0.001) and hepatic (p: 0.006) toxicities

  • -

    Haplotype C3435T, G2677T/A and C1236T: TTT ↑induction death (p: 0.020), ↑renal (p: 0.016) and hepatic (p < 0.001) toxicities.
Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: in GO arm CT/TT↑EFS at 5 years (p: 0.017)

  • -

    DFS: in GO arm CT/TT trend to ↑DFS at 5 years (p: 0.054)

  • -

    RR: in GO arm CT/TT ↓RR at 5 years (p: 0.003)
Short et al., 2020 [64] 104 68
(24–88)		 Caucasian (86%)
Black (13%)		 NR AML 82De novo: 43.9Secondary: 56.1 GO + DAC
  • -

    CR, ORR, CIR, OS, RFS: no influence
G1199A
rs2229109		 Green et al., 2012 [57] 100 63
(20–85)		 Caucasian
(Europe)		 Yes De novo (normal karyotype) Ara C + ANT or MIT +/or Others
  • -

    OS at 4 years(TX censured): GG suggestive ↓OS (p: 0.06)
Falk et al., 2014 [59] 3 201 59
(18–85)		 Caucasian
(Sweden)		 Yes De novo (normal karyotype) Ara C + DAUNO or IDA ± ETOP +/or Others
  • -

    CR, OS, EFS: no influence (similar results in FLT3 wild-type subgroup).
C174967T
rs6980101		 Kim YK et al., 2007 [67] 49 37
(17–69) 		Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA
  • -

    CR: ↑CT vs. CC (p: 0.03)

  • -

    OS, RFS, RR: no influence
G146792C
rs10256836		 Kim YK et al., 2007 [67] 49 37
(17–69) 		Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA
  • -

    CR: ↑GG vs. GC (p: 0.03)

  • -

    OS, RFS, RR: no influence
T134575A
rs17327442		 Kim YK et al., 2007 [67] 49 37
(17–69) 		Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA
  • -

    CR: ↑TT vs. TA (p: 0.01)

  • -

    OS, RFS, RR: no influence
A113516G
rs4148732		 Kim YK et al., 2007 [67] 49 37
(17–69) 		Asian
(South Korea)		 NR De novo (t (8,21) and inv (16)) Ara C + IDA
  • -

    CR: ↑AA vs. AG (p: 0.001)

  • -

    OS, RFS, RR: no influence
C193T
rs121918619		 Monzo et al., 2006 [67] 110 44
(16–60)		 Caucasian
(Spain)		 Yes De novo (intermediate cytogenetic risk) Ara C + IDA + ETOP
  • -

    RR: CC/CT ↑RR (p: 0.02)

  • -

    OS at 2 years: no influence (but affect in multivariable analysis, CC ↑OS)
Illet144Met Monzo et al., 2006 [68] 110 44
(16–60)		 Caucasian
(Spain)		 NR De novo (intermediate cytogenetic risk) Ara C + IDA + ETOP
  • -

    RR, OS: no influence
rs3842
(A>G)		 Cao et al., 2017 [20] 206 67.2
(22–98)		 Asian
(China)		 Yes De novo Ara C + ANT
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    RFS: no influence

  • -

    Toxicity: no influence
rs2235015
(G>T)		 Rafiee et al., 2019 [63] 942 9.7 (0–30) Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: in GO arm GG/GT ↓RR at 5 years (p: 0.016)
rs2235033
(T>C)		 Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: no influence
rs1922242
(A>T)		 Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: no influence
rs1922240
(T>C)		 Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: no influence
rs1989830
(C>T)		 Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: no influence
rs2235040
(G>A)		 Rafiee et al., 2019 [63] 942 9.7
(0–30)		 Caucasian (81%)
Black (13%)
Asian (5%)
Others (1%)		 Yes De novo Ara C + IDA + ETOP ± GO
  • -

    OS: no influence

  • -

    EFS: no influence

  • -

    DFS: no influence

  • -

    RR: no influence
ABCB11
rs4668115
(G>A)		 Drenberg et al., 2016 [13] 4 164 9.1
(0–21)		 White (70%)
Black (20%)
Others (10%)		 Yes De novo Ara C + DAUNO + ETOP + MIT
  • -

    OS: GG ↓OS (p: 0.03)

  • -

    EFS: GG ↓EFS (p: 0.05)
ABCC1
T2684C Mahjoubi et al., 2008 [82] 111 NR Arabs
(Iran)		 NR 52 AMLNR NR
  • -

    CR: no influence

  • -

    Expression of ABCC1 related to lower CR, drug sensitive and R/R rate
C2007T
rs2301666		 Mahjoubi et al., 2008 [82] 111 NR Arabs
(Iran)		 NR 52 AMLNR NR
  • -

    CR: no influence

  • -

    Expression of ABCC1 related to lower CR, drug sensitive and R/R rate
G2012T
rs45511401		 Mahjoubi et al., 2008 [82] 111 NR Arabs
(Iran)		 NR 52 AMLNR NR
  • -

    CR: no influence

  • -

    Expression of ABCC1 related to lower CR, drug sensitive and R/R rate
C2665T Mahjoubi et al., 2008 [82] 111 NR Arabs
(Iran)		 NR 52 AMLNR NR
  • -

    CR: no influence

  • -

    Expression of ABCC1 related to lower CR, drug sensitive and R/R rate
T825C
rs246221		 Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
T1062C
rs35587		 Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
G4002A
rs2230671		 Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence

  • -

    Toxicity: no influence
rs4148350
(G>T)		 Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: wild-type GG ↑hepatic severe toxicity grade 3–4 (p: 0.044)
rs129081
(C>G)		 Kunadt et al., 2020 [83] 5 160 46
(18–60)		 Caucasian
(Germany)		 Yes NK AMLDe novo: 93.1Secondary: 6.9 Ara C + DAUNO
  • -

    CR: no influence

  • -

    OS: GG↑OS at 5 years (p: 0.035)

  • -

    DFS: GG↑DFS at 5 years (p: 0.01)

  • -

    RR: no influence

  • -

    Toxicity: no influence
rs212090
(A>T)		 Cao et al., 2017 [20] 206 67.2
(22–98)		 Asian
(China)		 Yes De novo Ara C + ANT
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    RFS: no influence

  • -

    Toxicity: AT ↑gastrointestinal toxicity (p: 0.010)
Kunadt et al., 2020 [83] 5 160 46
(18–60)		 Caucasian
(Germany)		 Yes NK AMLDe novo: 93.1Secondary: 6.9 Ara C + DAUNO
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    DFS: TT ↓DFS at 5 years (p: 0.021)

  • -

    RR: no influence

  • -

    Toxicity: no influence
rs212091
(A>G)		 Cao et al., 2017 [20] 206 67.2
(22–98)		 Asian
(China)		 Yes De novo Ara C + ANT
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    RFS: no influence

  • -

    Toxicity: GG/AG ↓myelosuppression (p: 0.003)
Kunadt et al., 2020 [83] 5 160 46
(18–60)		 Caucasian
(Germany)		 Yes NK AMLDe novo: 93.1Secondary: 6.9 Ara C + DAUNO
  • -

    CR: no influence

  • -

    OS: GG ↓OS at 5 years (p: 0.006)

  • -

    DFS: GG ↓DFS at 5 years (p: 0.018)

  • -

    RR: no influence

  • -

    Toxicity: no influence
rs3743527
(C>T)		 Cao et al., 2017 [20] 206 67.2
(22–98)		 Asian
(China)		 Yes De novo Ara C + ANT
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    RFS: no influence

  • -

    Toxicity: TT ↑myelosuppression (p: 0.007)
rs4148380
(G>A)		 Cao et al., 2017 [20] 206 67.2
(22–98)		 Asian
(China)		 Yes De novo Ara C + ANT
  • -

    CR: no influence

  • -

    OS: no influence

  • -

    RFS: no influence

  • -

    Toxicity: no influence
ABCC2
G4544A
rs8187710		 Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: no influence
ABCC3
45 + 1226 (T>G)
rs4148405		 Yee et al., 2013 [16] 6 154 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): GG ↓DFS (p: 9.45 × 10−6, remained significant after Bonferroni correction). No influence in non-Caucasian cohort
Butrym et al., 2021 [85] 95 61
(22–90)		 Caucasian
(Poland)		 Yes De novo Ara C + DAUNO or low dose Ara C or AZA
  • -

    CR: no influence

  • -

    OS: G allele ↓OS (p: 0.017)
rs1989983
(G>A)		 Yee et al., 2013 [16] 6 54 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): AA ↓DFS (p: 0.0017). No influence in non-Caucasian cohort
rs2301835
(C>T)		 Yee et al., 2013 [16] 6 154 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): TT ↓DFS (p: 0.0029). No influence in non-Caucasian cohort
rs2277624
(A>G)		 Yee et al., 2013 [16] 6 154 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): AA ↓DFS (p: 0.004). No influence in non-Caucasian cohort
rs8079740
(A>G)		 Yee et al., 2013 [16] 6 154 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): GG ↓DFS (p: 0.0078). No influence in non-Caucasian cohort
rs757420
(T>C)		 Yee et al., 2013 [16] 6 154 NR Caucasian
(Europe)		 NR NR Ara C + ETOP + BUSUL (pre-TX)
  • -

    DFS (preTX): TT ↓DFS (p: 0.0079). No influence in non-Caucasian cohort
C211T
rs4793665		 Müller et al., 2008 [18] 139 46.3
(15–86)		 Jews (61.2%)
Arabs (38.8%)		 Yes De novo Ara C + ANT ± FLUDA ± MIT
  • -

    OS (TX censured): CC ↓OS (p: 0.018)
Butrym et al., 2021 [88] 95 61
(22–90)		 Caucasian
(Poland)		 Yes De novo Ara C + DAUNO or low dose Ara C or AZA
  • -

    CR: no influence

  • -

    OS: no influence
ABCG2
G34A
rs2231137		 Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 NR De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): GG ↓OS (p: 0.05)

  • -

    Toxicity: AA/AG ↑ risk of toxicity grade 3 or more
Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR: trend to GG ↑CR (p: 0.053). Mixed with ALL patients

  • -

    OS: GG↑OS (p < 0.001). Mixed with ALL patients

  • -

    DFS: GG↑DFS (p < 0.001). Mixed with ALL patients

  • -

    Haplotype GG (rs2231137) with CA (rs2231142) and CT (rs2231149) ↓DFS/OS (p < 0.001)
Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: no influence
C421A
rs2231142		 Müller et al., 2008 [18] 139 46.3
(15–86)		 Jews (61.2%)
Arabs (38.8%)		 Yes De novo Ara C + ANT ± FLUDA ± MIT
  • -

    OS (TX censured): no influence
Hampras et al., 2010 [56] 261 61.5
(20–85)		 Caucasian (86%)
Others (14%)
(USA)		 Yes De novo: 75Secondary: 25 Ara C + ANT
  • -

    OS (TX censured): no influence, but unadjusted HR shown AA ↓OS

  • -

    Toxicity: no influence
Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR: no influence.

  • -

    OS: CC↑OS (p < 0.05; lost in multivariate analysis). Mixed with ALL patients

  • -

    DFS: no influence. Mixed with ALL patients

  • -

    Haplotype GG (rs2231137) with CA (rs2231142) and CT (rs2231149) ↓DFS/OS (p < 0.001)
Tiribelli et al., 2013 [98] 125 59.2
(20–84)		 Caucasian
(Italy)		 Yes NR Ara C + IDA + FLUDA ± ETOP
  • -

    OS at 3 years: CC and low ABCG2 expression ↑OS (p: 0.02)

  • -

    DFS at 3 years: CC and low ABCG2 expression ↑DFS (p: 0.04)
Megías-Vericat et al., 2017 [62] 225 52.5
(16–78)		 Caucasian Yes De novo Ara C + IDA
  • -

    CR, induction death: no influence

  • -

    Toxicity: CA genotype ↑cardiac (p: 0.004) and lung (p: 0.038) toxicities
Ile619Ile
(C>T)		 Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR, OS, DFS: no influence. Mixed with ALL patients
rs2231149
(C>T)		 Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR: no influence. Mixed with ALL patients

  • -

    OS: CC↑OS (p < 0.01; lost in multivariate analysis). Mixed with ALL patients

  • -

    DFS: CC↑DFS (p < 0.05; lost in multivariate analysis). Mixed with ALL patients

  • -

    Haplotype GG (rs2231137) with CA (rs2231142) and CT (rs2231149) ↓DFS/OS (p < 0.001)
rs2231162
(C>T)		 Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR, OS, DFS: no influence. Mixed with ALL patients
rs2231164
(C>T)		 Wang et al., 2011 [97] 141 32
(5–70)		 Asian
(China)		 NR De novoMixed with ALL Ara C + DAUNO/MITO
  • -

    CR, OS, DFS: no influence. Mixed with ALL patients

Abbreviations: ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; AMSA: amsacrine; ANT: anthracycline; AZA: azacitidine; BH-AC: N4-behenoyl-1D-arabinofuranosycytosine; BUSUL: busulfan; CIR: cumulative incidence of relapse; CR: complete remission; DAC: decitabine; DAUNO: daunorubicin; DFS: disease-free survival; EFS: event-free survival; ETOP: etoposide; FLUDA: fludarabine; GO: gemtuzumab ozogamicin; HWE: Hardy–Weinberg equilibrium; IDA: idarubicin; MIT: mitoxantrone; NK: normal karyotype; NR: not reported; ORR: overall response rate; OS: overall survival; RFS: relapse-free survival; RR: rate of relapse; R/R: relapse/refractory; TX: hematologic transplant. 1—Allele frequency and treatment outcomes only reported in 115 patients for C1236T, 142 patients for G2677T/A and 130 patients for C3435T. 2—Allele frequency only reported in 103 patients and treatment outcomes only in 44 patients (AML M3 subtype, secondary AML and patients with comorbidities or poor performance status were excluded). 3—A total of 100 patients were previously collected and published in Green et al., 2012 [57]. 4—This study [13] analyzed 1936 SNPs of 225 genes with a multi-SNP-based approach (including ABC and SLC transporters). Only SNPs with significant results were cited. 5—This study [83] included 48 SNPs within 7 genes of 7 ABC transporters (ABCA2, ABCA3, ABCB1, ABCB2, ABCB5, ABCB7 and ABCC1), but only specified the SNPs with significant effect. 6—This study [16] analyzed 1659 SNPs of 42 genes with a multi-SNP-based approach. Only SNPs with significant results were cited.