PMID- 30669372
OWN - NLM
STAT- MEDLINE
DCOM- 20190501
LR  - 20230528
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 2
DP  - 2019 Jan 18
TI  - Targeting PI3K Signaling in Acute Lymphoblastic Leukemia.
LID - 10.3390/ijms20020412 [doi]
LID - 412
AB  - Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells 
      triggers intracellular signals regulating cell-adhesion-mediated drug resistance 
      (CAM-DR). Stromal cell protection of ALL cells has been shown to require active 
      AKT. In chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the 
      PI3K/AKT pathway is reported. A novel FDA-approved PI3Kdelta inhibitor, 
      CAL-101/idelalisib, leads to downregulation of p-AKT and increased apoptosis of 
      CLL cells. Recently, two additional PI3K inhibitors have received FDA approval. 
      As the PI3K/AKT pathway is also implicated in adhesion-mediated survival of ALL 
      cells, PI3K inhibitors have been evaluated preclinically in ALL. However, PI3K 
      inhibition has yet to be approved for clinical use in ALL. Here, we review the 
      role of PI3K in normal hematopoietic cells, and in ALL. We focus on summarizing 
      targeting strategies of PI3K in ALL.
FAU - Sanchez, Vanessa Edna
AU  - Sanchez VE
AD  - Department of Pathology, Keck School of Medicine of University of Southern 
      California, Los Angeles, CA 90033, USA. vanesses@usc.edu.
AD  - Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow 
      Transplantation, Children's Hospital Los Angeles, University of Southern 
      California, Los Angeles, CA 90027, USA. vanesses@usc.edu.
FAU - Nichols, Cydney
AU  - Nichols C
AUID- ORCID: 0000-0003-4024-5339
AD  - New York Medical College School of Medicine, Valhalla, NY 10595, USA. 
      cnichols5@student.nymc.edu.
FAU - Kim, Hye Na
AU  - Kim HN
AD  - Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow 
      Transplantation, Children's Hospital Los Angeles, University of Southern 
      California, Los Angeles, CA 90027, USA. hyekim@chla.usc.edu.
FAU - Gang, Eun Ji
AU  - Gang EJ
AD  - Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow 
      Transplantation, Children's Hospital Los Angeles, University of Southern 
      California, Los Angeles, CA 90027, USA. vanesses@usc.edu.
FAU - Kim, Yong-Mi
AU  - Kim YM
AD  - Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow 
      Transplantation, Children's Hospital Los Angeles, University of Southern 
      California, Los Angeles, CA 90027, USA. ymkim@chla.usc.edu.
LA  - eng
GR  - R01 CA172896/CA/NCI NIH HHS/United States
GR  - R25 CA225513/CA/NCI NIH HHS/United States
GR  - CA172896/NH/NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20190118
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Isoenzymes)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - B-Lymphocytes/drug effects/metabolism
MH  - Clinical Trials as Topic
MH  - Drug Evaluation, Preclinical
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Isoenzymes
MH  - *Molecular Targeted Therapy/adverse effects/methods
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*drug 
      therapy/*metabolism/mortality
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects
MH  - Treatment Outcome
PMC - PMC6358886
OTO - NOTNLM
OT  - PI3K/AKT
OT  - PI3Kdelta
OT  - acute lymphoblastic leukemia (ALL)
OT  - cell adhesion mediated drug resistance (CAM-DR)
COIS- The authors declare no conflict of interest.
EDAT- 2019/01/24 06:00
MHDA- 2019/05/02 06:00
PMCR- 2019/01/01
CRDT- 2019/01/24 06:00
PHST- 2018/12/14 00:00 [received]
PHST- 2019/01/13 00:00 [revised]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/01/24 06:00 [entrez]
PHST- 2019/01/24 06:00 [pubmed]
PHST- 2019/05/02 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - ijms20020412 [pii]
AID - ijms-20-00412 [pii]
AID - 10.3390/ijms20020412 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jan 18;20(2):412. doi: 10.3390/ijms20020412.