Biology session

ATP-binding cassette (ABC) transporters, present in all living organisms, take part in cell protection and metabolism. Their main task is to pump their substrates in the extracellular space with an ATP-dependent manner. ABCB1 and ABCG2 transporters appear to be expressed in hematopoietic stem cells, and presumed to play a protective role against a broad spectrum of toxic substrates. They are also responsible for the efflux of physiological substrates, such as steroids, and their expression may play a regulatory role in stem cells’ cell cycle. Both transporters participate in the absorption, distribution, metabolism, excretion of drugs and in the multidrug resistance during chemotherapy.

Our main question was that the common, functional polymorphisms of ABCB1 and ABCG2 transporters may have an effect on susceptibility to acute myeloid leukemia (AML), as well as influencing the clinical presentation and treatment outcome of the disease in humans.

We studied 389 AML patients and 202 healthy controls. The outcome of therapy were analysed for 307 patients younger than 60 years and treated with curative intention. Single nucleotide polymorphisms of ABCB1 (c.2677G>T/A and c.3435C>T) and ABCG2 (c.34G>A and c.421C>A) were analysed by Light Cycler melting curve technique.

Allele frequencies (AF) were not different in AML patients as a whole cohort compared to controls, but it is worth pointing that a rare haplotype of ABCB1 (2677G/3435T) was more frequent in the AML group (9.9 vs. 6.1%; p=0.017). AML subgroup analysis revealed that t(8;21)(q22;q22) translocation positive patients in ABCG2 c.34G>A variants showed higher AF compared to control individuals (18.4% vs. 4.0%; p=0.002). ABCB1 polymorphism tested in this study did not alter disease predisposition or treatment outcome. Among AML patients receiving daunorubicin and cytarabine treatment, ABCG2 c.421C>A carriers displayed longer survival compared to individuals carrying the major allele (48 month overall survival: 47±9% vs. 27±3%, p=0.027).

Our results suggest that a rare haplotype (2677G/3435T) of ABCB1 transporter has an effect on acute myeloid leukemia disease susceptibility and the c.421C>A variant of ABCG2 might influence treatment outcome depending on chemotherapy applied.