PMID- 33942222
OWN - NLM
STAT- MEDLINE
DCOM- 20211228
LR  - 20211228
IS  - 1699-3055 (Electronic)
IS  - 1699-048X (Linking)
VI  - 23
IP  - 10
DP  - 2021 Oct
TI  - Gene mutations in acute promyelocytic leukemia early death in patients treated 
      with arsenic trioxide alone.
PG  - 2171-2180
LID - 10.1007/s12094-021-02625-6 [doi]
AB  - PURPOSE: APL patients have recurrent alterations in FLT3, WT1, NRAS and KRAS. 
      Gene mutations have a strong potential for involvement in pathogenesis and may 
      have potential effects on the clinical manifestations. Gene mutations may even be 
      associated with early death (ED) in APL patients. However, there is little 
      published information on mutations in APL patients and whether they are 
      attributed to early death. METHODS: In this study, we retrospectively analyzed 
      the clinical data and gene mutations of 134 de novo APL patients. We detected the 
      gene mutations by next-generation sequencing (NGS) to investigate the genetic 
      predictors of early death in APL patients. According to the number of gene 
      mutations per patient, the 134 APL patients were divided into three groups. All 
      patients received arsenic trioxide (ATO) alone as induction therapy. The clinical 
      data and gene mutations were compared and analyzed. RESULTS: A total of 134 APL 
      patients were involved in the study. The clinical data of sex, WBC, PT, and DD, 
      UA, and LDH level were significantly different between the three groups 
      (P = 0.000, P = 0.000, P = 0.009, P = 0.020, P = 0.030, P = 0.001 and P = 0.014, 
      respectively). Meanwhile, among them, the Sanz risk stratification and early 
      death rate were significantly different (P = 0.001). The early death rate was 
      10.4%, and the median time to early death was 6.6 days (range 2-15 days). For the 
      next-generation sequencing, a mean of 1.28 +/- 1.06 mutations per patient was 
      detected (range: 0-5). The univariate and the multivariate regression analysis 
      showed that age > 50[HR = 1.666, CI (1.027-2.702), P = 0.039], high WBC count 
      [HR = 4.702, CI (1.026-21.543), P = 0.046] and low ALB levels [HR = 4.547, CI 
      (1.088-18.995), P = 0.038] were independent risk factors for early death in APL 
      patients. Furthermore, Kaplan-Meier survival analysis, univariate analysis, and 
      the multivariate regression analysis showed that patients with multiple gene 
      mutations [HR = 2.258, CI (1.115-4.571), P = 0.024], KRAS [HR = 5.136, CI 
      (1.356-19.455), P = 0.016] and/or GATA2 [HR = 4.070, CI (1.287-12.877), 
      P = 0.017] have a significantly higher early death rate. CONCLUSION: The results 
      of this investigation show that both molecular markers and clinical variables 
      should be used as potential predictors for early death in APL patients. Our 
      results suggested that age > 50, high WBC count, low ALB levels, and the presence 
      of multiple gene mutations, KRAS and/or GATA2 at the time of diagnosis were 
      independent risk factors for early death in APL patients. For these patients, 
      clinicians should be more cautious during the course of induction treatment.
CI  - (c) 2021. Federacion de Sociedades Espanolas de Oncologia (FESEO).
FAU - Chen, Xiaotong
AU  - Chen X
AD  - The first Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Fan, Shengjin
AU  - Fan S
AD  - The first Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Zhao, Yanqiu
AU  - Zhao Y
AD  - The first Affiliated Hospital of Harbin Medical University, Harbin, China.
FAU - Zhou, Jin
AU  - Zhou J
AUID- ORCID: 0000-0003-4367-0605
AD  - The first Affiliated Hospital of Harbin Medical University, Harbin, China. 
      zhoujin1111@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210503
PL  - Italy
TA  - Clin Transl Oncol
JT  - Clinical & translational oncology : official publication of the Federation of 
      Spanish Oncology Societies and of the National Cancer Institute of Mexico
JID - 101247119
RN  - 0 (Antineoplastic Agents)
RN  - 0 (GATA2 Transcription Factor)
RN  - 0 (GATA2 protein, human)
RN  - 0 (Genetic Markers)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/therapeutic use
MH  - Arsenic Trioxide/therapeutic use
MH  - Cause of Death
MH  - Child
MH  - Female
MH  - GATA2 Transcription Factor/genetics
MH  - Genes, ras
MH  - Genetic Markers
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Induction Chemotherapy/methods
MH  - Leukemia, Promyelocytic, Acute/blood/drug therapy/*genetics/*mortality
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Platelet Count
MH  - Prothrombin Time
MH  - Regression Analysis
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Survival Rate
MH  - Time Factors
MH  - Young Adult
OTO - NOTNLM
OT  - Acute promyelocytic leukemia
OT  - Early death
OT  - GATA2
OT  - Gene mutations
OT  - KRAS
OT  - Next-generation sequencing
EDAT- 2021/05/05 06:00
MHDA- 2021/12/29 06:00
CRDT- 2021/05/04 07:00
PHST- 2021/03/04 00:00 [received]
PHST- 2021/04/13 00:00 [accepted]
PHST- 2021/05/05 06:00 [pubmed]
PHST- 2021/12/29 06:00 [medline]
PHST- 2021/05/04 07:00 [entrez]
AID - 10.1007/s12094-021-02625-6 [pii]
AID - 10.1007/s12094-021-02625-6 [doi]
PST - ppublish
SO  - Clin Transl Oncol. 2021 Oct;23(10):2171-2180. doi: 10.1007/s12094-021-02625-6. 
      Epub 2021 May 3.