scholarly journals Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy

2013 ◽  
Vol 60 (8) ◽  
pp. 1287-1291 ◽  
Author(s):  
Adam J. Esbenshade ◽  
Jill H. Simmons ◽  
Tatsuki Koyama ◽  
Robert B. Lindell ◽  
Debra L. Friedman
Keyword(s):  
Insulin Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia

Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e19611-e19611
Author(s):  
A. J. Esbenshade ◽  
J. H. Simmons ◽  
T. Koyama ◽  
E. Koehler ◽  
R. B. Lindell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia

Effective VCR/DEX pulse maintenance therapy in the KYCCSG ALL-02 protocol for pediatric acute lymphoblastic leukemia

2015 ◽  
Vol 103 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Yasuhiro Okamoto ◽  
Yuki Koga ◽  
Jiro Inagaki ◽  
Shuichi Ozono ◽  
Koichiro Ueda ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia

scholarly journals The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 224
Author(s):  
Jae Min Lee ◽  
Ye Jee Shim ◽  
Do-Hoon Kim ◽  
Nani Jung ◽  
Jung-Sook Ha
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Febrile Neutropenia ◽  
Maintenance Therapy ◽  
Synergistic Effects ◽  
Lymphoblastic Leukemia ◽  
Dose Intensity ◽  
Genetic Variations ◽  
Allele Carrier ◽  
Clinical Effects ◽  
Pediatric Acute Lymphoblastic Leukemia

Mercaptopurine (MP) is a commonly used maintenance regimen for childhood acute lymphoblastic leukemia (ALL). However, 6-MP has a narrow therapeutic index, which causes dose-limiting toxicities in hematopoietic tissues. Recent studies reported several candidate pharmacogenetic markers such as TPMT, NUDT15, ITPA, and APEX1, which predict the possibility of 6-MP related toxicities. The aim of this study is to evaluate the effect of major variants of these genes on 6-MP intolerances and toxicities in pediatric acute lymphoblastic leukemia (ALL) patients. A total of 83 pediatric ALL patients were included (56 males and 27 females). The NUDT15 c.415C>T (rs116855232), NUDT15 c.55_56insGAGTCG (rs746071566), ITPA c.94C>A (rs1127354), ITPA c.IVS2+21A>C (rs7270101), APEX c.190A>G (rs2307486), and TPMT variants were analyzed by sanger sequencing. Correlations between indexes of 6-MP-related toxicities or 6-MP intolerance (absolute neutrophil count [ANC] at several time point, days of ANC < 1 × 103/mm3, days of ANC < 0.5 × 103/mm3, frequency of febrile neutropenia, maximum AST and ALT, 6-MP dose and 6-MP dose intensity during maintenance therapy) and genetic variations were analyzed. The NUDT15 c.415C>T allele carrier showed significantly low 6-MP doses at the final maintenance therapy period than the wild type carrier (p = 0.007). The 6-MP dose intensities at the sixth and final maintenance period were also significantly low in NUDT15 c.415C>T carriers (p = 0.003 and 0.008, respectively). However, indexes for neutropenia, days of febrile neutropenia, maximum AST, and ALT levels were not associated with the presence of c.415C>T as well as other analyzed variants. When analyzing the effect of the coexistence of NUDT15 c.415C>T and ITPA c.94C>A, no significant differences were found between the NUDT15 c.415C>T carrier and carrier with both variations. The NUDT15 c.415C>T was the most useful marker to predict 6-MP intolerance among analyzed variants in our study population. Although we could not find association of those variants with 6-MP induced toxicities and the synergistic effects of those variants, a well-planed larger scale study would be helpful in clarifying new candidates and their clinical effects.

scholarly journals Mutational patterns and clonal evolution from diagnosis to relapse in pediatric acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shumaila Sayyab ◽  
Anders Lundmark ◽  
Malin Larsson ◽  
Markus Ringnér ◽  
Sara Nystedt ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Large Scale ◽  
Somatic Mutations ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Point Mutations ◽  
Driver Genes ◽  
Protein Coding ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Evolutionary Trajectories

AbstractThe mechanisms driving clonal heterogeneity and evolution in relapsed pediatric acute lymphoblastic leukemia (ALL) are not fully understood. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients. Somatic point mutations and large-scale structural variants were called using individually matched remission samples as controls, and allelic expression of the mutations was assessed in ALL cells using RNA-sequencing. We observed an increased burden of somatic mutations at relapse, compared to diagnosis, and at second relapse compared to first relapse. In addition to 29 known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, we identified putative non-protein coding mutations in regulatory regions of seven additional genes that have not previously been described in ALL. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression from diagnosis to relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.

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