Journal of pediatric hematology/oncology · 2010
Multiplex reverse transcription-polymerase chain reaction as diagnostic molecular screening of 4 common fusion chimeric genes in Taiwanese children with acute lymphoblastic leukemia.
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Yang Yung-Li, Lin Shu-Rung, Chen Jiann-Shiuh, 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
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentCell LineageChildChild, PreschoolChimeraCore Binding Factor Alpha 2 SubunitFemaleFusion Proteins, bcr-ablGenetic TestingHumansInfantInfant, NewbornMaleMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPolymerase Chain ReactionPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisReverse Transcriptase Polymerase Chain ReactionRisk FactorsSensitivity and SpecificityTaiwanETS Translocation Variant 6 Protein