Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia.
Current prognostic factors for acute myeloblastic leukemia (AML) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment. Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses. We used the allelic discrimination method to identify polymorphisms in GSTT1, SULT1C2, CDA, SXR (drug metabolic pathways), XPD, XPA, XPG, ERCC1, TOP2A (DNA repair), VEGF (angiogenesis), and MDR1 (multidrug resistance) genes in 110 adult patients with intermediate-risk AML, enrolled in the CETLAM-99 prospective trial. A multivariate prognostic model adjusted for age, white blood cell (WBC) count, French-American-British group, cytogenetics, MLL rearrangement, internal tandem duplication of FLT3 (FLT3-ITD), induction courses to achieve complete remission, and germline polymorphisms, was used to detect independent risk factors associated with clinical outcome. This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles (RR = 14; P = .02). In the same model, increased relapse risk was associated with SULT1C2 heterozygosity (RR = 4.1; P = .004), FLT3-ITD (RR 3.3; P = .003), and MDR1 variant alleles (RR = 2.4; P = .02). Adverse prognostic variables for overall survival were XPA (RR = 3.4; P = .02) and MDR1 (RR = 2.1; P = .02) variant alleles, and WBC count (RR = 2.1; P = .02). These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML.
Monzo
Mariano
M
Hospital Clínic, Hospital Universitario de la Santa Creu i Sant Pau, Barcelona, Spain.
Brunet
Salut
S
Urbano-Ispizua
Alvaro
A
Navarro
Alfons
A
Perea
Granada
G
Esteve
Jordi
J
Artells
Rosa
R
Granell
Miquel
M
Berlanga
Juan
J
Ribera
Josep M
JM
Bueno
Javier
J
Llorente
Andreu
A
Guardia
Ramon
R
Tormo
Mar
M
Torres
Pio
P
Nomdedéu
Josep F
JF
Montserrat
Emili
E
Sierra
Jordi
J
D000328:Adult; D000483:Alleles; D018572:Disease-Free Survival; D005260:Female; D006579:Heterozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D007958:Leukocyte Count; D008297:Male; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome
D009363:Neoplasm Proteins