British journal of haematology, 2014-12, Vol.167 (5), p.671-680
2014
Details
- Autor(en) / Beteiligte
- Titel
- Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild‐type de novo AML patients with normal karyotype
- Ist Teil von
- British journal of haematology, 2014-12, Vol.167 (5), p.671-680
- Ort / Verlag
- Oxford: Blackwell
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- Wiley Online Library All Journals
- Beschreibungen/Notizen
- Summary Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi‐drug transporter P‐glycoprotein, and overall survival (OS) in normal karyotype (NK)‐AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK‐AML patients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated. FLT3 wild‐type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0·017. There was also an inferior outcome in FLT3 wild‐type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0·039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild‐type group, which may contribute to future individualizing of treatment strategies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1048, 1365-2141eISSN: 1365-2141DOI: 10.1111/bjh.13097Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_130134492
- Format
- –
- Schlagworte
- ABCB1, acute myeloid leukaemia, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, anthracyclines, ATP Binding Cassette Transporter, Sub-Family B - genetics, ATP Binding Cassette Transporter, Sub-Family B - metabolism, Biological and medical sciences, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Disease-Free Survival, Female, FLT3, fms-Like Tyrosine Kinase 3 - genetics, fms-Like Tyrosine Kinase 3 - metabolism, Hematologi, Hematologic and hematopoietic diseases, Hematology, Humans, Leukemia, Myeloid, Acute - genetics, Leukemia, Myeloid, Acute - metabolism, Leukemia, Myeloid, Acute - mortality, Leukemia, Myeloid, Acute - therapy, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, Male, Medical sciences, Medicin och hälsovetenskap, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, single nucleotide polymorphism, Survival Rate, Tumors