PMID- 35733807
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2296-2360 (Print)
IS  - 2296-2360 (Electronic)
IS  - 2296-2360 (Linking)
VI  - 10
DP  - 2022
TI  - Gene Mutations Related to Glucocorticoid Resistance in Pediatric Acute 
      Lymphoblastic Leukemia.
PG  - 831229
LID - 10.3389/fped.2022.831229 [doi]
LID - 831229
AB  - OBJECTIVE: To investigate the correlation between gene mutations and 
      glucocorticoid resistance in pediatric acute lymphoblastic leukemia (ALL). 
      METHODS: A total of 71 children with ALL admitted to our center between September 
      2019 and September 2021 were enrolled. DNA obtained from bone marrow or 
      peripheral blood samples at initial diagnosis was used for genetic testing via 
      whole exome sequencing. Meanwhile, patient clinical information was collected. 
      Subsequently, the correlations of gene mutations with clinical features and 
      glucocorticoid resistance were analyzed. RESULTS: Of the 71 children enrolled, 61 
      (85.9%) had B-cell ALL (B-ALL) and 10 (14.1%) had T-cell ALL (T-ALL). The five 
      genes with the highest mutation frequency in B-ALL were TTN (24.4%), FLT3 
      (14.6%), TP53 (14.6%), MUC16 (9.8%), and EPPK1 (9.8%). In contrast, those with 
      the highest frequency in T-ALL were NOTCH1 (54.5%), FBXW7 (27.3%), TTN (27.3%), 
      MUC16 (27.3%), and PHF6 (18.2%). Upon statistical analysis, TTN and NOTCH1 
      mutations were found to be associated with prednisone resistance. Further, TTN 
      and MUC16 mutations were associated with a lower age at diagnosis, and NOTCH1 
      mutations were associated with T-ALL in female patients. Leukocyte counts and LDH 
      levels did not differ based on the presence of any common gene mutation, and no 
      association between these gene mutations and overall survival was observed. 
      CONCLUSIONS: Our study is the first to demonstrate the association between TTN 
      mutation and glucocorticoid resistance in ALL. Our findings could guide 
      strategies for overcoming drug resistance and aid in the development of drug 
      targets.
CI  - Copyright (c) 2022 Zhang, Zeng, Wang, Pan, Li, Feng and Yang.
FAU - Zhang, JinFang
AU  - Zhang J
AD  - Department of Paediatric Hematology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Zeng, LingJi
AU  - Zeng L
AD  - Department of Hematology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, China.
FAU - Wang, YuLian
AU  - Wang Y
AD  - Department of Hematology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, China.
FAU - Pan, JianWei
AU  - Pan J
AD  - Department of Paediatric Hematology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Li, XingDong
AU  - Li X
AD  - Department of Paediatric Hematology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Feng, Bei
AU  - Feng B
AD  - Department of Paediatric Hematology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Yang, Quan
AU  - Yang Q
AD  - Department of Paediatric Hematology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220606
PL  - Switzerland
TA  - Front Pediatr
JT  - Frontiers in pediatrics
JID - 101615492
PMC - PMC9207762
OTO - NOTNLM
OT  - NOTCH1
OT  - TTN
OT  - acute lymphoblastic leukemia
OT  - drug resistance
OT  - gene mutation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/24 06:00
MHDA- 2022/06/24 06:01
PMCR- 2022/06/06
CRDT- 2022/06/23 02:29
PHST- 2021/12/08 00:00 [received]
PHST- 2022/05/13 00:00 [accepted]
PHST- 2022/06/23 02:29 [entrez]
PHST- 2022/06/24 06:00 [pubmed]
PHST- 2022/06/24 06:01 [medline]
PHST- 2022/06/06 00:00 [pmc-release]
AID - 10.3389/fped.2022.831229 [doi]
PST - epublish
SO  - Front Pediatr. 2022 Jun 6;10:831229. doi: 10.3389/fped.2022.831229. eCollection 
      2022.