Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia

Yung Li Yang, Shu Rung Lin, Chien-Hsu Chen, Chih Cheng Hsiao, Kai Hsin Lin, Jiunn Ming Sheen, Chao-Neng Cheng, Kang Hsi Wu, Shu Wha Lin, Sung Liang Yu, Hsuan Yu Chen, Meng Yao Lu, Hsiu Hao Chang, Ching Tzu Yen, Jing Fang Lin, Ying Hui Su, Ya Ping Li, Chien Yu Lin, Shiann Tarng Jou, Dong Tsamn Lin

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Abstract

Background The classification of B-lineage acute lymphoblastic leukemia (ALL) by specific chromosomal translocations has prognostic implications for risk-directed therapy. Reverse transcription-polymerase chain reaction (RT-PCR) assay is a useful tool for detecting fusion transcripts from common chromosomal translocations of ALL cells. Methods Multiplex RT-PCR and nested-PCR assays were used to detect ALL-type BCR-ABL1 transcripts of the t(9; 22), TCF-PBX1 transcripts of t(1; 19), the MLL-AF4 transcripts of t(4; 11), and 2 variants of ETV6-RUNX1 of the cryptic t(12; 21) in 148 leukemic samples upon diagnosis. The patients received risk-directed protocols of the Taiwan Pediatric Oncology Group-ALL-2002 that consisted of multiple chemotherapeutic agents of different intensities. Event-free survival (EFS) and overall survival (OS) rates were analyzed for genetic abnormalities detected by multiplex PCR and conventional cytogenetic analysis by the Kaplan-Meier method, and compared with the Mantel-Haenszel test. The Cox proportional hazards model was implemented to identify independent prognostic factors for EFS and OS. Results In this cohort of Taiwanese children, the relative frequencies of the 4 translocations of B-lineage ALL were 8% with ALL-type t(9; 22)/BCR-ABL1, 4% with (1; 19)/TCF-PBX1, 2% with t(4; 11)/MLL-AF4, and 17.6% with t(12; 21)/ETV6-RUNX1. Patients with t(12; 21)/ETV6-RUNX1 fusion, hyperdiploidy, and t(1; 19)/TCF-PBX1 fusion had the most favorable outcomes, whereas those with the t(9; 22)/BCR-ABL1 fusion or t(4; 11) and other MLL gene rearrangement had poor prognosis (P< 0.001 for EFS and OS). BCR-ABL1, MLL gene rearrangement, and very high-risk group were independent prognostic factors after Cox regression analysis. Conclusions The biological factors of leukemia cells are associated with treatment outcomes in childhood ALL. Multiplex RT-PCR assay is an efficient and sensitive diagnostic tool that may improve the ability to accurately and rapidly risk-stratify children with ALL.

Original languageEnglish
Pages (from-to)e323-e330
JournalJournal of Pediatric Hematology/Oncology
Volume32
Issue number8
DOIs
Publication statusPublished - 2010 Jan 1

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Molecular Pathology
Gene Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Reverse Transcription
Polymerase Chain Reaction
Disease-Free Survival
Genetic Translocation
Gene Rearrangement
Polyploidy
Survival
Cytogenetic Analysis
Multiplex Polymerase Chain Reaction
Biological Factors
Taiwan
Proportional Hazards Models
Leukemia
Survival Rate
Regression Analysis
Pediatrics

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Yang, Yung Li ; Lin, Shu Rung ; Chen, Chien-Hsu ; Hsiao, Chih Cheng ; Lin, Kai Hsin ; Sheen, Jiunn Ming ; Cheng, Chao-Neng ; Wu, Kang Hsi ; Lin, Shu Wha ; Yu, Sung Liang ; Chen, Hsuan Yu ; Lu, Meng Yao ; Chang, Hsiu Hao ; Yen, Ching Tzu ; Lin, Jing Fang ; Su, Ying Hui ; Li, Ya Ping ; Lin, Chien Yu ; Jou, Shiann Tarng ; Lin, Dong Tsamn. / Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia. In: Journal of Pediatric Hematology/Oncology. 2010 ; Vol. 32, No. 8. pp. e323-e330.
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title = "Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia",
abstract = "Background The classification of B-lineage acute lymphoblastic leukemia (ALL) by specific chromosomal translocations has prognostic implications for risk-directed therapy. Reverse transcription-polymerase chain reaction (RT-PCR) assay is a useful tool for detecting fusion transcripts from common chromosomal translocations of ALL cells. Methods Multiplex RT-PCR and nested-PCR assays were used to detect ALL-type BCR-ABL1 transcripts of the t(9; 22), TCF-PBX1 transcripts of t(1; 19), the MLL-AF4 transcripts of t(4; 11), and 2 variants of ETV6-RUNX1 of the cryptic t(12; 21) in 148 leukemic samples upon diagnosis. The patients received risk-directed protocols of the Taiwan Pediatric Oncology Group-ALL-2002 that consisted of multiple chemotherapeutic agents of different intensities. Event-free survival (EFS) and overall survival (OS) rates were analyzed for genetic abnormalities detected by multiplex PCR and conventional cytogenetic analysis by the Kaplan-Meier method, and compared with the Mantel-Haenszel test. The Cox proportional hazards model was implemented to identify independent prognostic factors for EFS and OS. Results In this cohort of Taiwanese children, the relative frequencies of the 4 translocations of B-lineage ALL were 8{\%} with ALL-type t(9; 22)/BCR-ABL1, 4{\%} with (1; 19)/TCF-PBX1, 2{\%} with t(4; 11)/MLL-AF4, and 17.6{\%} with t(12; 21)/ETV6-RUNX1. Patients with t(12; 21)/ETV6-RUNX1 fusion, hyperdiploidy, and t(1; 19)/TCF-PBX1 fusion had the most favorable outcomes, whereas those with the t(9; 22)/BCR-ABL1 fusion or t(4; 11) and other MLL gene rearrangement had poor prognosis (P< 0.001 for EFS and OS). BCR-ABL1, MLL gene rearrangement, and very high-risk group were independent prognostic factors after Cox regression analysis. Conclusions The biological factors of leukemia cells are associated with treatment outcomes in childhood ALL. Multiplex RT-PCR assay is an efficient and sensitive diagnostic tool that may improve the ability to accurately and rapidly risk-stratify children with ALL.",
author = "Yang, {Yung Li} and Lin, {Shu Rung} and Chien-Hsu Chen and Hsiao, {Chih Cheng} and Lin, {Kai Hsin} and Sheen, {Jiunn Ming} and Chao-Neng Cheng and Wu, {Kang Hsi} and Lin, {Shu Wha} and Yu, {Sung Liang} and Chen, {Hsuan Yu} and Lu, {Meng Yao} and Chang, {Hsiu Hao} and Yen, {Ching Tzu} and Lin, {Jing Fang} and Su, {Ying Hui} and Li, {Ya Ping} and Lin, {Chien Yu} and Jou, {Shiann Tarng} and Lin, {Dong Tsamn}",
year = "2010",
month = "1",
day = "1",
doi = "10.1097/MPH.0b013e3181ed1655",
language = "English",
volume = "32",
pages = "e323--e330",
journal = "Journal of Pediatric Hematology/Oncology",
issn = "1077-4114",
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}

Yang, YL, Lin, SR, Chen, C-H, Hsiao, CC, Lin, KH, Sheen, JM, Cheng, C-N, Wu, KH, Lin, SW, Yu, SL, Chen, HY, Lu, MY, Chang, HH, Yen, CT, Lin, JF, Su, YH, Li, YP, Lin, CY, Jou, ST & Lin, DT 2010, 'Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia', Journal of Pediatric Hematology/Oncology, vol. 32, no. 8, pp. e323-e330. https://doi.org/10.1097/MPH.0b013e3181ed1655

Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia. / Yang, Yung Li; Lin, Shu Rung; Chen, Chien-Hsu; Hsiao, Chih Cheng; Lin, Kai Hsin; Sheen, Jiunn Ming; Cheng, Chao-Neng; Wu, Kang Hsi; Lin, Shu Wha; Yu, Sung Liang; Chen, Hsuan Yu; Lu, Meng Yao; Chang, Hsiu Hao; Yen, Ching Tzu; Lin, Jing Fang; Su, Ying Hui; Li, Ya Ping; Lin, Chien Yu; Jou, Shiann Tarng; Lin, Dong Tsamn.

In: Journal of Pediatric Hematology/Oncology, Vol. 32, No. 8, 01.01.2010, p. e323-e330.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia

AU - Yang, Yung Li

AU - Lin, Shu Rung

AU - Chen, Chien-Hsu

AU - Hsiao, Chih Cheng

AU - Lin, Kai Hsin

AU - Sheen, Jiunn Ming

AU - Cheng, Chao-Neng

AU - Wu, Kang Hsi

AU - Lin, Shu Wha

AU - Yu, Sung Liang

AU - Chen, Hsuan Yu

AU - Lu, Meng Yao

AU - Chang, Hsiu Hao

AU - Yen, Ching Tzu

AU - Lin, Jing Fang

AU - Su, Ying Hui

AU - Li, Ya Ping

AU - Lin, Chien Yu

AU - Jou, Shiann Tarng

AU - Lin, Dong Tsamn

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background The classification of B-lineage acute lymphoblastic leukemia (ALL) by specific chromosomal translocations has prognostic implications for risk-directed therapy. Reverse transcription-polymerase chain reaction (RT-PCR) assay is a useful tool for detecting fusion transcripts from common chromosomal translocations of ALL cells. Methods Multiplex RT-PCR and nested-PCR assays were used to detect ALL-type BCR-ABL1 transcripts of the t(9; 22), TCF-PBX1 transcripts of t(1; 19), the MLL-AF4 transcripts of t(4; 11), and 2 variants of ETV6-RUNX1 of the cryptic t(12; 21) in 148 leukemic samples upon diagnosis. The patients received risk-directed protocols of the Taiwan Pediatric Oncology Group-ALL-2002 that consisted of multiple chemotherapeutic agents of different intensities. Event-free survival (EFS) and overall survival (OS) rates were analyzed for genetic abnormalities detected by multiplex PCR and conventional cytogenetic analysis by the Kaplan-Meier method, and compared with the Mantel-Haenszel test. The Cox proportional hazards model was implemented to identify independent prognostic factors for EFS and OS. Results In this cohort of Taiwanese children, the relative frequencies of the 4 translocations of B-lineage ALL were 8% with ALL-type t(9; 22)/BCR-ABL1, 4% with (1; 19)/TCF-PBX1, 2% with t(4; 11)/MLL-AF4, and 17.6% with t(12; 21)/ETV6-RUNX1. Patients with t(12; 21)/ETV6-RUNX1 fusion, hyperdiploidy, and t(1; 19)/TCF-PBX1 fusion had the most favorable outcomes, whereas those with the t(9; 22)/BCR-ABL1 fusion or t(4; 11) and other MLL gene rearrangement had poor prognosis (P< 0.001 for EFS and OS). BCR-ABL1, MLL gene rearrangement, and very high-risk group were independent prognostic factors after Cox regression analysis. Conclusions The biological factors of leukemia cells are associated with treatment outcomes in childhood ALL. Multiplex RT-PCR assay is an efficient and sensitive diagnostic tool that may improve the ability to accurately and rapidly risk-stratify children with ALL.

AB - Background The classification of B-lineage acute lymphoblastic leukemia (ALL) by specific chromosomal translocations has prognostic implications for risk-directed therapy. Reverse transcription-polymerase chain reaction (RT-PCR) assay is a useful tool for detecting fusion transcripts from common chromosomal translocations of ALL cells. Methods Multiplex RT-PCR and nested-PCR assays were used to detect ALL-type BCR-ABL1 transcripts of the t(9; 22), TCF-PBX1 transcripts of t(1; 19), the MLL-AF4 transcripts of t(4; 11), and 2 variants of ETV6-RUNX1 of the cryptic t(12; 21) in 148 leukemic samples upon diagnosis. The patients received risk-directed protocols of the Taiwan Pediatric Oncology Group-ALL-2002 that consisted of multiple chemotherapeutic agents of different intensities. Event-free survival (EFS) and overall survival (OS) rates were analyzed for genetic abnormalities detected by multiplex PCR and conventional cytogenetic analysis by the Kaplan-Meier method, and compared with the Mantel-Haenszel test. The Cox proportional hazards model was implemented to identify independent prognostic factors for EFS and OS. Results In this cohort of Taiwanese children, the relative frequencies of the 4 translocations of B-lineage ALL were 8% with ALL-type t(9; 22)/BCR-ABL1, 4% with (1; 19)/TCF-PBX1, 2% with t(4; 11)/MLL-AF4, and 17.6% with t(12; 21)/ETV6-RUNX1. Patients with t(12; 21)/ETV6-RUNX1 fusion, hyperdiploidy, and t(1; 19)/TCF-PBX1 fusion had the most favorable outcomes, whereas those with the t(9; 22)/BCR-ABL1 fusion or t(4; 11) and other MLL gene rearrangement had poor prognosis (P< 0.001 for EFS and OS). BCR-ABL1, MLL gene rearrangement, and very high-risk group were independent prognostic factors after Cox regression analysis. Conclusions The biological factors of leukemia cells are associated with treatment outcomes in childhood ALL. Multiplex RT-PCR assay is an efficient and sensitive diagnostic tool that may improve the ability to accurately and rapidly risk-stratify children with ALL.

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DO - 10.1097/MPH.0b013e3181ed1655

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SP - e323-e330

JO - Journal of Pediatric Hematology/Oncology

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