ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of Brazilian acute myeloid leukemia patients

Scheiner, Marcos Antônio Maurício; Vasconcelos, Flavia da Cunha; Matta, Roberta Rodrigues da; Figueira, Reinaldo Dal Bello; Maia, Raquel Ciuvalschi

doi:10.1007/s00432-012-1170-x

Cited by 18 publications

(9 citation statements)

References 43 publications

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“…In addition, a strong link between ABCB1 genetic variants and P-gp expression with poor survival in AML patients has been reported 51,52. Scheiner et al51 examined the relationship between ABCB1 polymorphism (C1236T, C3435T) and P-gp expression activity in 109 Brazilian AML patients to understand the possible relationship between these factors and their clinical significance.…”

Section: Abcb1 Variants and Aml Treatmentmentioning

confidence: 99%

“…Scheiner et al51 examined the relationship between ABCB1 polymorphism (C1236T, C3435T) and P-gp expression activity in 109 Brazilian AML patients to understand the possible relationship between these factors and their clinical significance. They reported achievement of better 5-year OS and 5-year EFS rates in patients presenting with genetic variant CC in exon 12, followed by those presenting the variant CT in exon 26.…”

Section: Abcb1 Variants and Aml Treatmentmentioning

confidence: 99%

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<em>ABCB1</em> genetic variants in leukemias: current insights into treatment outcomes

Ankathil¹

2017

PGPM

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Despite improvements in treatment of different types of leukemia, not all patients respond optimally for a particular treatment. Some treatments will work better for some, while being harmful or ineffective for others. This is due to genetic variation in the form of single-nucleotide polymorphisms (SNPs) that affect gene expression or function and cause inherited interindividual differences in the metabolism and disposition of drugs. Drug transporters are one of the determinants governing the pharmacokinetic profile of chemotherapeutic drugs. The ABCB1 transporter gene transports a wide range of drugs, including drugs used in leukemia treatment. Polymorphisms in the ABCB1 gene do affect intrinsic resistance and pharmacokinetics of several drugs used in leukemia treatment protocols and thereby affect the efficacy of treatment and event-free survival. This review focuses on the impact of three commonly occurring SNPs (1236C>T, 2677G>T/A, and 3435C>T) of ABCB1 on treatment response of various types of leukemia. From the literature available, some of the genotypes and haplotypes of these SNPs have been found to be potential determinants of interindividual variability in drug disposition and pharmacologic response in different types of leukemia. However, due to inconsistencies in the results observed across the studies, additional studies, considering novel genomic methodologies, comprehensive definition of clinical phenotypes, adequate sample size, and uniformity in all the confounding factors, are warranted.

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Section: Abcb1 Variants and Aml Treatmentmentioning

confidence: 99%

Section: Abcb1 Variants and Aml Treatmentmentioning

confidence: 99%

<em>ABCB1</em> genetic variants in leukemias: current insights into treatment outcomes

Ankathil¹

2017

PGPM

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“…P-gp is lowly expressed in tumor cells with drug susceptibility and highly expressed in drug-resistant tumor cells 12. Scheiner et al13 detected the P-gp expression level in 109 patients with acute myeloid leukemia, and the results showed that the expression of P-gp was negatively correlated with the treatment remission rate, hence, it was the poor prognostic factor. Zhu et al14 used immunohistochemical method to detect the expression of P-gp in 82 patients with breast cancer and analyzed the relationship between the clinicopathological features and the prognosis of the patients, the results showed that the P-gp expression level was closely associated with the prognosis of patients with breast cancer, the higher the expression level, the lower the survival rate.…”

Section: Discussionmentioning

confidence: 99%

Influence of MDR1 methylation on the curative effect of interventional embolism chemotherapy for cervical cancer

Huang

Zhang

Shen

et al. 2016

TCRM

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BackgroundMulti-drug resistance (MDR) is the main cause of tumor failure to chemotherapy. This study aims to explore the influence of MDR1 methylation on curative effect of interventional embolism chemotherapy for cervical cancer.MethodsSixty-seven patients with cervical cancer receiving embolism chemotherapy were selected, and 45 normal cervical tissues were included as a control. Immunohistochemistry was used to detect the level of P-glycoprotein (P-gp) in cervical cancer, and to make an analysis compared with normal tissues. The methylation status of the MDR1 gene promoter region 16 CpG units was analyzed by using kilobase-specific cracking and matrix-assisted laser desorption ionization time of flight mass spectrometry.ResultsThe results indicated that the positive expression rates of P-gp were 0% (0/45) in normal cervical tissue, and 61.19% (41/67) and 77.61% (52/67) before and after interventional embolism chemotherapy in cervical cancer tissues, respectively. There were significant differences compared with normal cervical tissues (χ2=4.2523, 0.0392). The positive expression rate of P-gp before chemotherapy was negatively correlated with efficacy of chemotherapy (r=−0.340, P=0.005). Methylation rate of 13 CpG units in normal tissues was significantly greater than cervical tissues (P<0.05). In cervical cancer tissue, methylation rate of six CpG units before interventional embolism chemotherapy was higher than after chemotherapy, but that of one CpG unit was lower than after chemotherapy (P<0.05). The methylation rate of one CpG unit with effective chemotherapy before chemotherapy was significantly higher than ineffective chemotherapy (P<0.05), and the other CpG units were similar (P>0.05).ConclusionP-gp expression level coded by MDR1, methylation status of partial MDR1 gene promoter regions CpG island, is closely related to the efficacy of interventional embolism chemotherapy for cervical cancer before the operation.

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“…Uważa się, że obecność tego polimorfizmu nie wpływa na ekspresję genu ABCB1, jednakże obecność formy polimorficznej może hamować wiązanie się z kompleksem rybosomowym, a przez to wpływać na składanie domeny 6 (TM6) niezbędnej do łączenia się glikoproteiny P z substratem. W związku z tym u form heterozygotycznych 1236CT obserwuje się najwyższą aktywność glikoproteiny P [25].…”

Section: Wstępunclassified

“…Zamiana cytozyny na tyminę w pozycji 3435 nie powoduje zmiany w sekwencji aminokwasowej białka, jednakże sugeruje się, że polimorfizm ten może wpływać na stabilność mRNA, a tym samym ilość glikoproteiny P [29,30]. Wykazano, że homozygoty polimorficzne 3435TT mają znacznie niższy poziom glikoproteiny P niż homozygoty dzikie (3435CC) oraz heterozygoty (3435CT) [31][32][33], jednak najwyższą aktywność białka obserwuje się u osób z formą heterozygotyczną 3435CT [25].…”

Section: Wstępunclassified

Contribution of ABCB1 gene polymorphisms to breast cancer cells response to chemotherapy

Hołysz¹,

Rubiś²

2013

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StreszczenieKażdego roku odnotowuje się 11 000 nowych przypadków zachorowań na raka piersi, a prawie połowa chorych umiera. Tak wysoka umieralność może być spowodowana zbyt późnym rozpoznaniem choroby, brakiem specyficznych i skutecznych leków, a także wystąpieniem zjawiska oporności wielolekowej (multiple drug resistance -MDR) w komórkach nowotworowych. Podstawowym mechanizmem wywołującym to zjawisko jest nadekspresja i zwiększona aktywność transporterów błonowych, z których większość należy do nadrodziny transporterów ABC (ATP binding casette). Spośród tych białek najlepiej poznanym jest glikoproteina P, produkt ekspresji genu ABCB1, odpowiedzialna m.in. za usuwanie ksenobiotyków i leków poza obszar komórki. Szerokie spektrum substratowe glikoproteiny P obejmuje: ksenobiotyki oraz leki cytotoksyczne, inhibitory białek, immunosupresanty, steroidy, statyny, blokery kanału wapniowego, beta-blokery, leki antyhistaminowe, przeciwdepresyjne oraz przeciwwymiotne. W sekwencji genu ABCB1 opisano szereg polimorfizmów, spośród których najwięk-sze znaczenie kliniczne mają trzy -zamiana cytozyny na tyminę w pozycji 1236 egzonu 12 (C1236T, rs1128503), zamiana w egzonie 21 G2677A/T (rs2032582) oraz w egzonie 26 C3435T (rs1045642). Występowanie tych polimorfizmów może wpływać na zmianę ekspresji genu ABCB1 (C3435T), strukturę glikoproteiny P (G2677T/A) czy zdolność wiązania się białka z substratem (C1236T). Jak się podejrzewa, obecność tych polimorfizmów może w efekcie modyfikować odpowiedź komórek nowotworowych na chemioterapię. Niniejsza praca opisuje modulujący wpływ polimorfizmów genu ABCB1 na odpowiedź komórek raka piersi na chemioterapię.Słowa kluczowe: rak piersi, glikoproteina P, chemioterapia.

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ABCB1 genetic variation and P-glycoprotein expression/activity in a cohort of Brazilian acute myeloid leukemia patients

Abstract: Polymorphisms in the ABCB1 gene and the levels of Pgp expression could be useful to identify prognostic in AML patients.

Cited by 18 publications

References 43 publications

<em>ABCB1</em> genetic variants in leukemias: current insights into treatment outcomes

<em>ABCB1</em> genetic variants in leukemias: current insights into treatment outcomes

Influence of MDR1 methylation on the curative effect of interventional embolism chemotherapy for cervical cancer

Contribution of ABCB1 gene polymorphisms to breast cancer cells response to chemotherapy

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