Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Zhiheng Cheng; Yifeng Dai; Yifan Pang; Yang Jiao; Hongmian Zhao; Sun Wu; Lingxiu Zhang; Yuan Zhang; Xiufeng Wang; Lihua Wang; Dong Ma; Tong Qin; Ning Hu; Yijie Zhang; Kai Hu; Qingyi Zhang; Jinlong Shi; Lin Fu

doi:10.1159/000491065

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Zhiheng Cheng, Yifeng Dai, Yifan Pang, Yang Jiao, Hongmian Zhao, Sun Wu, Lingxiu Zhang, Yuan Zhang, Xiufeng Wang, Lihua Wang, Dong Ma, Tong Qin, Ning Hu, Yijie Zhang, Kai Hu, Qingyi Zhang, Jinlong Shi, Lin Fu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Basel

Original language	English
Pages (from-to)	1853-1861
Number of pages	9
Journal	Cellular physiology and biochemistry
Volume	47
Issue number	5
DOIs	https://doi.org/10.1159/000491065
Publication status	Published - 2018

Keywords

Acute myeloid leukemia
M0 and M1
Next generation sequencing
Mutational spectrum
Prognosis
PREDICTS FAVORABLE PROGNOSIS
GENE-MUTATIONS
CLASSIFICATION
IMPACT
NPM1
AML
INTERMEDIATE
KARYOTYPE
RELEVANCE
PARADIGM

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Cheng, Z., Dai, Y., Pang, Y., Jiao, Y., Zhao, H., Wu, S., Zhang, L., Zhang, Y., Wang, X., Wang, L., Ma, D., Qin, T., Hu, N., Zhang, Y., Hu, K., Zhang, Q., Shi, J., & Fu, L. (2018). Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1. Cellular physiology and biochemistry, 47(5), 1853-1861. https://doi.org/10.1159/000491065

@article{511882b02fd942cfb755a105b2c349c0,

title = "Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1",

abstract = "Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Basel",

keywords = "Acute myeloid leukemia, M0 and M1, Next generation sequencing, Mutational spectrum, Prognosis, PREDICTS FAVORABLE PROGNOSIS, GENE-MUTATIONS, CLASSIFICATION, IMPACT, NPM1, AML, INTERMEDIATE, KARYOTYPE, RELEVANCE, PARADIGM",

author = "Zhiheng Cheng and Yifeng Dai and Yifan Pang and Yang Jiao and Hongmian Zhao and Sun Wu and Lingxiu Zhang and Yuan Zhang and Xiufeng Wang and Lihua Wang and Dong Ma and Tong Qin and Ning Hu and Yijie Zhang and Kai Hu and Qingyi Zhang and Jinlong Shi and Lin Fu",

year = "2018",

doi = "10.1159/000491065",

language = "English",

volume = "47",

pages = "1853--1861",

journal = "Cellular physiology and biochemistry",

issn = "1015-8987",

publisher = "KARGER",

number = "5",

}

Cheng, Z, Dai, Y, Pang, Y, Jiao, Y, Zhao, H, Wu, S, Zhang, L, Zhang, Y, Wang, X, Wang, L, Ma, D, Qin, T, Hu, N, Zhang, Y, Hu, K, Zhang, Q, Shi, J & Fu, L 2018, 'Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1', Cellular physiology and biochemistry, vol. 47, no. 5, pp. 1853-1861. https://doi.org/10.1159/000491065

TY - JOUR

T1 - Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

AU - Cheng, Zhiheng

AU - Dai, Yifeng

AU - Pang, Yifan

AU - Jiao, Yang

AU - Zhao, Hongmian

AU - Wu, Sun

AU - Zhang, Lingxiu

AU - Zhang, Yuan

AU - Wang, Xiufeng

AU - Wang, Lihua

AU - Ma, Dong

AU - Qin, Tong

AU - Hu, Ning

AU - Zhang, Yijie

AU - Hu, Kai

AU - Zhang, Qingyi

AU - Shi, Jinlong

AU - Fu, Lin

PY - 2018

Y1 - 2018

N2 - Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Basel

AB - Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Basel

KW - Acute myeloid leukemia

KW - M0 and M1

KW - Next generation sequencing

KW - Mutational spectrum

KW - Prognosis

KW - PREDICTS FAVORABLE PROGNOSIS

KW - GENE-MUTATIONS

KW - CLASSIFICATION

KW - IMPACT

KW - NPM1

KW - AML

KW - INTERMEDIATE

KW - KARYOTYPE

KW - RELEVANCE

KW - PARADIGM

U2 - 10.1159/000491065

DO - 10.1159/000491065

M3 - Article

SN - 1015-8987

VL - 47

SP - 1853

EP - 1861

JO - Cellular physiology and biochemistry

JF - Cellular physiology and biochemistry

IS - 5

ER -

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

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