PMID- 35409154
OWN - NLM
STAT- MEDLINE
DCOM- 20220413
LR  - 20220416
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 7
DP  - 2022 Mar 30
TI  - Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The 
      State-of-the-Art Knowledge and Future Prospects.
LID - 10.3390/ijms23073795 [doi]
LID - 3795
AB  - Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. 
      Despite the enormous progress in ALL therapy, resulting in achieving a 5-year 
      survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate 
      is still being pursued. A typical ALL treatment includes three phases: remission 
      induction and consolidation and maintenance, preceded by a prednisone prephase. 
      Poor prednisone response (PPR) is defined as the presence of >/=1.0 x 10(9) 
      blasts/L in the peripheral blood on day eight of therapy and results in 
      significantly frequent relapses and worse outcomes. Hence, identifying risk 
      factors of steroid resistance and finding methods of overcoming that resistance 
      may significantly improve patients' outcomes. A mitogen-activated protein 
      kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a 
      particularly attractive target, as its activation leads to steroid resistance via 
      a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is 
      crucial in the steroid-induced cell death. Several mutations causing activation 
      of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway 
      mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in 
      precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance 
      the results of dexamethasone therapy in preclinical ALL studies. This report 
      summarizes steroids' mechanism of action, resistance to treatment, and prospects 
      of steroids therapy in pediatric ALL.
FAU - Kosmider, Kamil
AU  - Kosmider K
AUID- ORCID: 0000-0003-3844-8831
AD  - Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University 
      of Lublin, Gebali 6, 20-093 Lublin, Poland.
FAU - Karska, Katarzyna
AU  - Karska K
AD  - Department of Pediatric Hematology, Oncology and Transplantology, Medical 
      University of Lublin, Gebali 6, 20-093 Lublin, Poland.
FAU - Kozakiewicz, Agata
AU  - Kozakiewicz A
AD  - Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University 
      of Lublin, Gebali 6, 20-093 Lublin, Poland.
FAU - Lejman, Monika
AU  - Lejman M
AD  - Laboratory of Genetic Diagnostics, Medical University of Lublin, Gebali 6, 20-093 
      Lublin, Poland.
FAU - Zawitkowska, Joanna
AU  - Zawitkowska J
AUID- ORCID: 0000-0001-7207-156X
AD  - Department of Pediatric Hematology, Oncology and Transplantology, Medical 
      University of Lublin, Gebali 6, 20-093 Lublin, Poland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220330
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Glucocorticoids)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Glucocorticoids/pharmacology/therapeutic use
MH  - Humans
MH  - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/pathology
MH  - *Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism
MH  - Prednisone/therapeutic use
PMC - PMC8999045
OTO - NOTNLM
OT  - BH3 mimetics
OT  - IL-7
OT  - JAK/STAT pathway
OT  - MAPK/ERK pathway
OT  - Ras pathway
OT  - acute lymphoblastic leukemia
OT  - glucocorticoids
OT  - poor prednisone response
OT  - proteasome inhibitors
OT  - steroids
COIS- The authors declare no conflict of interest.
EDAT- 2022/04/13 06:00
MHDA- 2022/04/14 06:00
PMCR- 2022/03/30
CRDT- 2022/04/12 01:12
PHST- 2022/01/22 00:00 [received]
PHST- 2022/03/20 00:00 [revised]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/04/12 01:12 [entrez]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2022/03/30 00:00 [pmc-release]
AID - ijms23073795 [pii]
AID - ijms-23-03795 [pii]
AID - 10.3390/ijms23073795 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Mar 30;23(7):3795. doi: 10.3390/ijms23073795.