Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine.
BACKGROUND
Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug.


METHODS
AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival.


RESULTS
Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival.


CONCLUSIONS
These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.
Myrna
M
Candelaria
Carmen
C
Corrales-Alfaro
Olga
O
Gutiérrez-Hernández
José
J
Díaz-Chavez
Juan
J
Labardini-Méndez
Silvia
S
Vidal-Millán
Luis A
LA
Herrera
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use*; D003842:Deoxycytidine Kinase / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; D003561:Cytarabine; D004317:Doxorubicin; D003842:Deoxycytidine Kinase