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Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL.

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Nat Med2015PMID 25962120PMC4670083stubpubmedProvenance
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PubMed
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Sep 8, 2026
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normalized (units and labels harmonized; values unchanged)
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ING-CIVIC-20260908-000001
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Linked entities (25)

How each link was made (MeSH, dictionary, registry reference, curation…) and whether it has been validated. Candidate links are not counted in entity statistics.

Validated 25

Curated evidence

Evidence citing this paper (46)

civicProvenance
Source
CIViC — Clinical Interpretation of Variants in Cancer
Dataset
CIViC evidence items
Version
civic-2026-09-08
Retrieved
Sep 8, 2026
Layer
normalized (units and labels harmonized; values unchanged)
Evidence
expert curation
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CC0 1.0
PMID
25962120
Run
ING-CIVIC-20260908-000001
Open at source
CuratedShowing 1–46 of 46 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.
TherapyCancerTypeLevelDirection · significanceRating (1–5)StatusEvidenceSource
NT5C2 R238W1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance2submitted
EID8077

Lentiviral-mediated overexpression of NT5C2 R238W (a relapse specific variant) in Reh cells resulted in resistance against thiopurines (mercaptopurine and thioguanine) compared to NT5C2 wildtype overe… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 A190T4
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticBSupports Poor Outcome3accepted
EID7888

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 A190T was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Lometrexol + MercaptopurineCombinationB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Sensitivity Response3accepted
EID7913

Treatment with the GART inhibitor, Lometrexol (de novo purine synthesis inhibitor), sensitized Reh cells overexpressing PRPS1 A190T to mercaptopurine (6-MP) as evidenced by significant reduction of th… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance5accepted
EID7909

Lentiviral-mediated overexpression of PRPS1 A190T in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7928

Lentiviral-mediated overexpression of PRPS1 A190T in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 A190V2
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7887

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 A190V was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID7908

Lentiviral-mediated overexpression of PRPS1 A190V in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 A87T1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance4accepted
EID7919

Lentiviral-mediated overexpression of PRPS1 A87T in Reh cells resulted in similar cytotoxic response (IC50 and apoptosis %) compared to controls (empty vector and wildtype PRPS1 overexpression) after … (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 C77S1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7916

Lentiviral-mediated overexpression of PRPS1 C77S in Reh cells resulted in similar cytotoxic response to controls (empty vector and overexpression of known reduced-function PRPS1 mutants) after exposur… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 D139G1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7915

Lentiviral-mediated overexpression of PRPS1 D139G in Reh cells resulted in similar cytotoxic response to controls (empty vector and overexpression of known reduced-function PRPS1 mutants) after exposu… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 D183E3
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7879

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 D183E was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7900

Lentiviral-mediated overexpression of PRPS1 D183E in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7927

Lentiviral-mediated overexpression of PRPS1 D183E in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 D183H1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID7897

Lentiviral-mediated overexpression of D183H in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apoptosis co… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 G174E2
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7881

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 G174E was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID7902

Lentiviral-mediated overexpression of PRPS1 G174E in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 I72V1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7917

Lentiviral-mediated overexpression of PRPS1 I72V in Reh cells resulted in similar cytotoxic response to controls (empty vector and overexpression of known reduced-function PRPS1 mutants) after exposur… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 K176N3
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7880

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 K176N was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7901

Lentiviral-mediated overexpression of PRPS1 K176N in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7926

Lentiviral-mediated overexpression of PRPS1 K176N in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 L191F4
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7878

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 L191F was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
CytarabineB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Sensitivity Response2accepted
EID7911

Lentiviral-mediated overexpression of PRPS1 L191F in Reh cells resulted in sensitivity to cytarabine (Ara-C) treatment as indicated by reduced cell viability and IC50 compared to empty vector and wild… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7899

Lentiviral-mediated overexpression of PRPS1 L191F in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7923

Lentiviral-mediated overexpression of PRPS1 L191F in Reh cells resulted no difference in response to Methotrexate, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS1 overexpres… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 M115T1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance4accepted
EID7920

Lentiviral-mediated overexpression of PRPS1 M115T in Reh cells resulted in similar cytotoxic response (IC50 and apoptosis %) compared to controls (empty vector and wildtype PRPS1 overexpression) after… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 MUTATION1
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticBSupports Poor Outcome4accepted
EID7871

Sequencing revealed relapse specific PRPS1 mutations in 24/358 (6.7%) relapsed childhood B-ALL cases derived from multiple cohorts. In the Chinese cohort, 18/138 (13%) cases harbored relapse specific … (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 N114D2
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7883

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 N114D was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4submitted
EID7904

Lentiviral-mediated overexpression of PRPS1 N114D in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 N144S4
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7882

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 N144S was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
CytarabineB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Sensitivity Response2accepted
EID7910

Lentiviral-mediated overexpression of PRPS1 N144S in Reh cells resulted in sensitivity to cytarabine (Ara-C) treatment as indicated by reduced cell viability and IC50 compared to empty vector and wild… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7903

Lentiviral-mediated overexpression of PRPS1 N144S in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7930

Lentiviral-mediated overexpression of PRPS1 N144S in Reh cells resulted no difference in response to Methotrexate, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS1 overexpres… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 S103I2
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7884

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 S103I was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7905

Lentiviral-mediated overexpression of PRPS1 S103I in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 S103N3
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7885

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 S103N was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7906

Lentiviral-mediated overexpression of PRPS1 S103N in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7925

Lentiviral-mediated overexpression of PRPS1 S103N in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 S103T4
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7886

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 S103T was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Lometrexol + MercaptopurineCombinationB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Sensitivity Response3submitted
EID7912

Treatment with the GART inhibitor, Lometrexol (de novo purine synthesis inhibitor), sensitized Reh cells overexpressing PRPS1 S103T to 6-MP as evidenced by significant reduction of the cell line's 6-M… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance5accepted
EID7907

Lentiviral-mediated overexpression of PRPS1 S103T in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7924

Lentiviral-mediated overexpression of PRPS1 S103T in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 T303S3
(prognostic)B Lymphoblastic Leukemia/LymphomaCURATED_BROADERPrognosticCSupports Poor Outcome3submitted
EID7877

PRPS1 exons were sequenced in the diagnosis and relapse samples of 358 B-Cell Childhood Acute Lymphoblastic Leukemia relapse patients (138 Chinese and 220 German). PRPS1 T303S was detected only at rel… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDSupports Resistance4accepted
EID7898

Lentiviral-mediated overexpression of PRPS1 T303S in Reh cells resulted in significant resistance against mercaptopurine (6-MP) and thioguanine (6-TG) as indicated by IC50 increases and reduced apopto… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7929

Lentiviral-mediated overexpression of PRPS1 T303S in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 V53A1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3accepted
EID7918

Lentiviral-mediated overexpression of PRPS1 V53A in Reh cells resulted in similar cytotoxic response to controls (empty vector and overexpression of known reduced-function PRPS1 mutants) after exposur… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic
PRPS1 Y311C1
Mercaptopurine + ThioguanineSubstitutesB Lymphoblastic Leukemia/LymphomaCURATED_BROADERPredictiveDDoes Not Support Resistance3submitted
EID7914

Lentiviral-mediated overexpression of PRPS1 Y311C in Reh cells resulted in similar cytotoxic response to controls (empty vector and overexpression of known reduced-function PRPS1 mutants) after exposu… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic