DNA variants in DHFR gene and response to treatment in children with childhood B ALL: revisited in AIEOP-BFM protocol

被引：11

作者：

Ceppi, Francesco ^{[1
,2
]}

Gagne, Vincent ^{[3
]}

Douyon, Laurance ^{[3
]}

Quintin, Camille J. ^{[3
]}

Colombini, Antonella ^{[4
]}

Parasole, Rosanna ^{[5
]}

Buldini, Barbara ^{[6
]}

Basso, Giuseppe ^{[6
]}

Conter, Valentino ^{[4
]}

Cazzaniga, Giovanni ^{[7
]}

Krajinovic, Maja ^{[3
,8
,9
]}

机构：

[1] Univ Lausanne Hosp, Dept Woman Mother Child, Div Pediat, Pediat Hematol Oncol Unit, CH-1004 Lausanne, Switzerland

[2] Univ Lausanne Hosp, Dept Woman Mother Child, Div Pediat, Pediat Hematol Oncol Res Lab, CH-1004 Lausanne, Switzerland

[3] CHU St Justine Res Ctr, Charles Bruneau Canc Ctr, Montreal, PQ H3T 1C5, Canada

[4] Univ Milano Bicocca, Osped S Gerardo, Dept Pediat, I-20835 Monza, Italy

[5] Santobono Pausilipon Hosp, Dept Pediat Hematooncol, I-80129 Naples, Italy

[6] Univ Padua, Dept Woman & Child Hlth, Lab Haematol Oncol, I-35128 Padua, Italy

[7] Univ Milano Bicocca, Dept Pediat, Ctr Ric Tettamanti, I-20835 Monza, Italy

[8] Univ Montreal, Dept Pediat, Fac Med, Montreal, PQ H4A 3J1, Canada

[9] Univ Montreal, Fac Med, Dept Pharmacol & Physiol, Montreal, PQ, Canada

来源：

PHARMACOGENOMICS | 2018年 / 19卷 / 02期

关键词：

childhood ALL; dihydrofolate reductase polymorphisms; treatment outcome; ACUTE LYMPHOBLASTIC-LEUKEMIA; DIHYDROFOLATE-REDUCTASE GENE; FOLATE CARRIER GENE; THIOPURINE METHYLTRANSFERASE; METHOTREXATE RESISTANCE; MAINTENANCE THERAPY; POLYMORPHISMS; PHARMACOGENETICS; RISK; SURVIVAL;

D O I：

10.2217/pgs-2017-0153

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. Methods: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. Results: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). Conclusion: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.

引用

页码：105 / 112

页数：8

共 29 条

[1] DNA Variants in Region for Noncoding Interfering Transcript of Dihydrofolate Reductase Gene and Outcome in Childhood Acute Lymphoblastic Leukemia [J].

Al-Shakfa, Fidaa ;

Dulucq, Stephanie ;

Brukner, Ivan ;

Milacic, Iva ;

Ansari, Marc ;

Beaulieu, Patrick ;

Moghrabi, Albert ;

Laverdiere, Caroline ;

Sallan, Stephen E. ;

Silverman, Lewis B. ;

Neuberg, Donna ;

Kutok, Jeffery L. ;

Sinnett, Daniel ;

Krajinovic, Maja .

CLINICAL CANCER RESEARCH, 2009, 15 (22) :6931-6938

[2] Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia [J].

Ansari, Marc ;

Sauty, Geraldine ;

Labuda, Malgorzata ;

Gagne, Vincent ;

Laverdiere, Caroline ;

Moghrabi, Albert ;

Sinnett, Daniel ;

Krajinovic, Maja .

BLOOD, 2009, 114 (07) :1383-1386

[3] The 5′-untransiated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major (core) promoter [J].

Blume, SW ;

Meng, Z ;

Shrestha, K ;

Snyder, RC ;

Emanuel, PD .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2003, 88 (01) :165-180

[4] Incorporation of Pharmacogenomics into Routine Clinical Practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process [J].

Caudle, Kelly E. ;

Klein, Teri E. ;

Hoffman, James M. ;

Mueller, Daniel J. ;

Whirl-Carrillo, Michelle ;

Gong, Li ;

McDonagh, Ellen M. ;

Sangkuhl, Katrin ;

Thorn, Caroline F. ;

Schwab, Matthias ;

Agundez, Jose A. G. ;

Freimuth, Robert R. ;

Huser, Vojtech ;

Lee, Ming Ta Michael ;

Iwuchukwu, Otito F. ;

Crews, Kristine R. ;

Scott, Stuart A. ;

Wadelius, Mia ;

Swen, Jesse J. ;

Tyndale, Rachel F. ;

Stein, C. Michael ;

Roden, Dan ;

Relling, Mary V. ;

Williams, Marc S. ;

Johnson, Samuel G. .

CURRENT DRUG METABOLISM, 2014, 15 (02) :209-217

[5] Acute lymphoblastic leukaemia: a model for the pharmacogenomics of cancer therapy [J].

Cheok, MH ;

Evans, WE .

NATURE REVIEWS CANCER, 2006, 6 (02) :117-129

[6] Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study [J].

Conter, Valentino ;

Valsecchi, Maria Grazia ;

Parasole, Rosanna ;

Putti, Maria Caterina ;

Locatelli, Franco ;

Barisone, Elena ;

Lo Nigro, Luca ;

Santoro, Nicola ;

Arico, Maurizio ;

Ziino, Ottavio ;

Pession, Andrea ;

Testi, Anna Maria ;

Micalizzi, Concetta ;

Casale, Fiorina ;

Zecca, Marco ;

Casazza, Gabriella ;

Tamaro, Paolo ;

La Barba, Gaetano ;

Notarangelo, Lucia Dora ;

Silvestri, Daniela ;

Colombini, Antonella ;

Rizzari, Carmelo ;

Biondi, Andrea ;

Masera, Giuseppe ;

Basso, Giuseppe .

BLOOD, 2014, 123 (10) :1470-1478

[7] Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study [J].

Conter, Valentino ;

Bartram, Claus R. ;

Valsecchi, Maria Grazia ;

Schrauder, Andre ;

Panzer-Gruemayer, Renate ;

Moericke, Anja ;

Arico, Maurizio ;

Zimmermann, Martin ;

Mann, Georg ;

De Rossi, Giulio ;

Stanulla, Martin ;

Locatelli, Franco ;

Basso, Giuseppe ;

Niggli, Felix ;

Barisone, Elena ;

Henze, Guenter ;

Ludwig, Wolf-Dieter ;

Haas, Oskar A. ;

Cazzaniga, Giovanni ;

Koehler, Rolf ;

Silvestri, Daniela ;

Bradtke, Jutta ;

Parasole, Rosanna ;

Beier, Rita ;

van Dongen, Jacques J. M. ;

Biondi, Andrea ;

Schrappe, Martin .

BLOOD, 2010, 115 (16) :3206-3214

[8] DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL [J].

Dulucq, Stephanie ;

St-Onge, Genevieve ;

Gagne, Vincent ;

Ansari, Marc ;

Sinnett, Daniel ;

Labuda, Damian ;

Moghrabi, Albert ;

Krajinovic, Maja .

BLOOD, 2008, 111 (07) :3692-3700

[9] Dihydrofolate Reductase Genetic Polymorphisms Affect Methotrexate Dose Requirements in Pediatric Patients With Acute Lymphoblastic Leukemia on Maintenance Therapy [J].

Gervasini, Guillermo ;

de Murillo, Silvia G. ;

Jimenez, Mercedes ;

de la Maya, Maria D. ;

Vagace, Jose M. .

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2017, 39 (08) :589-595

[10] AMPLIFICATION OF THE DIHYDROFOLATE-REDUCTASE GENE IS A MECHANISM OF ACQUIRED-RESISTANCE TO METHOTREXATE IN PATIENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA AND IS CORRELATED WITH P53 GENE-MUTATIONS [J].

GOKER, E ;

WALTHAM, M ;

KHERADPOUR, A ;

TRIPPETT, T ;

MAZUMDAR, M ;

ELISSEYEFF, Y ;

SCHNIEDERS, B ;

STEINHERZ, P ;

TAN, C ;

BERMAN, E ;

BERTINO, JR .

BLOOD, 1995, 86 (02) :677-684

← 1 2 3 →