Multidrug resistance 1 gene expression and AgNOR in childhood acute leukemias

Balamurugan, Subramani; Sugapriya, D.; Shanthi, Palanivelu; Thilaka, V.; Venkatadesilalu, S.; Pushpa, V.; M, Madhavan

doi:10.1007/s12288-008-0002-2

Cited by 2 publications

(2 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ATP-binding cassette sub-family B member 1 ( ABCB1 ) gene encodes for P-glycoprotein, an ATP-de pendent transmembrane efflux-pump. It trans ports xenobiotics out of cells, but also prevents the entry of toxic metabolites (11). Some tumours that are resistant to chemotherapy have ABCB1 over-expressed.…”

Section: Introductionmentioning

confidence: 99%

Variants in TPMT, ITPA, ABCC4 And ABCB1 Genes as Predictors of 6-Mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia

Milošević¹,

Kotur²,

Krstovski³

et al. 2018

Journal of Medical Biochemistry

View full text Add to dashboard Cite

SummaryAcute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, and a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in the maintenance phase of treatment for children with acute lymphoblastic leukemia. For those patients, TPMT genotype- tailored 6-mercaptopurine therapy is already implemented in the treatment protocols. We investigated the role of TPMT, ITPA, ABCC4 and ABCB1 genetic variants as predictors of outcome and 6-mercaptopurine induced toxicity during the maintenance phase of treatment in pediatric acute lymphoblastic leukemia. Sixty-eight children with acute lymphoblastic leukemia were enrolled in this study. Patients have been treated according to ALL IC-BFM 2002 or ALL IC-BFM 2009 protocols. Toxicity and adverse events have been monitored via surrogate markers (off-therapy weeks, episodes of leu - ko penia and average 6-mercaptopurine dose) and a prob- abilistic model was employed to predict overall 6-mercaptopurine related toxicity. We confirmed that patients with acute lymphoblastic leukemia that carry inactive TPMT allele(s) require 6- mercaptopurine dose reduction. ITPA and ABCC4 genetic variants failed to show an association with 6-mercapto - purine induced toxicity during the maintenance phase. Carriers of ABCB1 variant allele experienced greater hepatotoxicity. The probabilistic model Neural net which considered all the analysed genetic variants was assessed to be the best prediction model. It was able to discriminate ALL patients with good and poor 6-mercaptopurin tolerance in 71% of cases (AUC=0.71). This study contributes to the design of a panel of pharmacogenetic markers for predicting thiopurineinduced toxicity in pediatric ALL.

show abstract

Section: Introductionmentioning

confidence: 99%

Variants in TPMT, ITPA, ABCC4 And ABCB1 Genes as Predictors of 6-Mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia

Milošević¹,

Kotur²,

Krstovski³

et al. 2018

Journal of Medical Biochemistry

View full text Add to dashboard Cite

show abstract

“…MDR1 expression has been associated with a more unfavourable course (Dhooge et al, 2002), increased risk of relapse (Goasguen et al, 1996) and lower survival (Casale et al, 2004). Others found no effect of MDR1 expression on outcome (Kakihara et al, 1999;Plasschaert et al, 2003;Balamurugan et al, 2007).…”

Section: Review ª 2016 John Wiley and Sons Ltdmentioning

confidence: 99%

Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia

2016

View full text Add to dashboard Cite

Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients.

show abstract

Multidrug resistance 1 gene expression and AgNOR in childhood acute leukemias

Cited by 2 publications

References 20 publications

Variants in TPMT, ITPA, ABCC4 And ABCB1 Genes as Predictors of 6-Mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia

Variants in TPMT, ITPA, ABCC4 And ABCB1 Genes as Predictors of 6-Mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia

Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia

Contact Info

Product

Resources

About