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Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide.


ABSTRACT:

Background

Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL.

Methods

We included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or -TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2.

Results

More high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease-free survival in both training (HR = 6.761, 95% CI 2.179-20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089-14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS.

Conclusion

In an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL.

SUBMITTER: Shen Y 

PROVIDER: S-EPMC4535155 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide.

Shen Yang Y   Fu Ya-Kai YK   Zhu Yong-Mei YM   Lou Yin-Jun YJ   Gu Zhao-Hui ZH   Shi Jing-Yi JY   Chen Bing B   Chen Chao C   Zhu Hong-Hu HH   Hu Jiong J   Zhao Wei-Li WL   Mi Jian-Qing JQ   Chen Li L   Zhu Hong-Ming HM   Shen Zhi-Xiang ZX   Jin Jie J   Wang Zhen-Yi ZY   Li Jun-Min JM   Li Jun-Min JM   Chen Zhu Z   Chen Sai-Juan SJ  

EBioMedicine 20150412 6


<h4>Background</h4>Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL.<h4>Methods</h4>We included a consecutive series of 266 cases as training group  ...[more]

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