Response to glucocorticoids and toxicity in childhood acute lymphoblastic leukemia: Role of polymorphisms of genes involved in glucocorticoid response

2009 ◽  
Vol 53 (6) ◽  
pp. 984-991 ◽  
Author(s):  
Sara Marino ◽  
Federico Verzegnassi ◽  
Paolo Tamaro ◽  
Gabriele Stocco ◽  
Fiora Bartoli ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Glucocorticoid Response

scholarly journals Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia

2018 ◽  
Vol 52 (3) ◽  
pp. 296-306 ◽  
Author(s):  
Vladimir Gasic ◽  
Branka Zukic ◽  
Biljana Stankovic ◽  
Dragana Janic ◽  
Lidija Dokmanovic ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Initial Phase ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Induction Treatment ◽  
Glucocorticoid Response ◽  
Blast Count

AbstractBackgroundResponse to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1,GSTsandABCB1) that could contribute to improvement of GC response through personalization of GC therapy.MethodsRetrospective study enrolling 122 ALL patients was carried out to analyze variants ofNR3C1(rs33389, rs33388 and rs6198),GSTT1(null genotype),GSTM1(null genotype),GSTP1(rs1695 and rs1138272) andABCB1(rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology. The marker of GC response was blast count per microliter of peripheral blood on treatment day 8. We carried out analysis in which cut-off value for GC response was 1000 (according to Berlin-Frankfurt-Munster [BFM] protocol), as well as 100 or 0 blasts per microliter.ResultsCarriers of rareNR3C1rs6198 GG genotype were more likely to have blast count over 1000, than the non-carriers (p = 0.030).NR3C1CAA (rs33389-rs33388-rs6198) haplotype was associated with blast number below 1000 (p = 0.030).GSTP1GC haplotype carriers were more likely to have blast number below 1000 (p = 0.036), below 100 (p = 0.028) and to be blast negative (p = 0.054), whileGSTP1GT haplotype and rs1138272 T allele carriers were more likely to be blasts positive (p = 0.034 and p = 0.024, respectively).ABCB1CGT (rs1128503-rs2032582-rs1045642) haplotype carriers were more likely to be blast positive (p = 0.018).ConclusionsOur results have shown thatNR3C1rs6198 variant andGSTP1rs1695-rs1138272 haplotype are the most promising pharmacogenomic markers of GC response in ALL patients.

scholarly journals TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4252-4258 ◽  
Author(s):  
TW McLean ◽  
S Ringold ◽  
D Neuberg ◽  
K Stegmaier ◽  
R Tantravahi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocation ◽  
Fusion Transcript ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Childhood All ◽  
Polymerase Chain ◽  
B Lineage

Abstract Polymerase chain reaction-based screening of childhood acute lymphoblastic leukemia (ALL) samples showed that a TEL/AML1 fusion transcript was detected in 27% of all cases, representing the most common known gene rearrangement in childhood cancer. The TEL/AML1 fusion results from a t(12;21)(p13;q22) chromosomal translocation, but was undetectable at the routine cytogenetic level. TEL/AML1-positive patients had exclusively B-lineage ALL, and most patients were between the ages of 2 and 9 years at diagnosis. Only 3/89 (3.4%) adult ALL patients were TEL/AML1-positive. Most importantly, TEL/AML1-positive children had a significantly lower rate of relapse compared with TEL/AML1-negative patients (0/22 v 16/54, P = .004). Co- immunoprecipitation experiments demonstrated that TEL/AML-1 formed homodimers in vitro, and heterodimerized with the normal TEL protein when the two proteins were expressed together. The elucidation of the precise mechanism of transformation by TEL/AML1 and the role of TEL/AML1 testing in the treatment of childhood ALL will require additional studies.

scholarly journals Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0180488 ◽  
Author(s):  
Natalie P. Archer ◽  
Virginia Perez-Andreu ◽  
Ulrik Stoltze ◽  
Michael E. Scheurer ◽  
Anna V. Wilkinson ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Association Study ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Family Based
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