PMID- 24904821
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140624
LR  - 20211021
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 4
DP  - 2014
TI  - Role of integrin alpha4 in drug resistance of leukemia.
PG  - 99
LID - 10.3389/fonc.2014.00099 [doi]
LID - 99
AB  - Chemotherapeutic drug resistance in acute lymphoblastic leukemia (ALL) is a 
      significant problem, resulting in poor responsiveness to first-line treatment or 
      relapse after transient remission. Classical anti-leukemic drugs are non-specific 
      cell cycle poisons; some more modern drugs target oncogenic pathways in leukemia 
      cells, although in ALL these do not play a very significant role. By contrast, 
      the molecular interactions between microenvironment and leukemia cells are often 
      neglected in the design of novel therapies against drug resistant leukemia. It 
      was shown however, that chemotherapy resistance is promoted in part through 
      cell-cell contact of leukemia cells with bone marrow (BM) stromal cells, also 
      called cell adhesion-mediated drug resistance (CAM-DR). Incomplete response to 
      chemotherapy results in persistence of resistant clones with or without 
      detectable minimal residual disease (MRD). Approaches for how to address CAM-DR 
      and MRD remain elusive. Specifically, studies using anti-functional antibodies 
      and genetic models have identified integrin alpha4 as a critical molecule 
      regulating BM homing and active retention of normal and leukemic cells. 
      Pre-clinical evidence has been provided that interference with alpha4-mediated 
      adhesion of ALL cells can sensitize them to chemotherapy and thus facilitate 
      eradication of ALL cells in an MRD setting. To this end, Andreeff and colleagues 
      recently provided evidence of stroma-induced and alpha4-mediated nuclear 
      factor-kappaB signaling in leukemia cells, disruption of which depletes leukemia 
      cells of strong survival signals. We here review the available evidence 
      supporting the targeting of alpha4 as a novel strategy for treatment of drug 
      resistant leukemia.
FAU - Shishido, Stephanie
AU  - Shishido S
AD  - Division of Hematology and Oncology, Department of Pediatrics, Children's 
      Hospital Los Angeles, University of Southern California Keck School of Medicine , 
      Los Angeles, CA , USA.
FAU - Bonig, Halvard
AU  - Bonig H
AD  - Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood 
      Service Baden-Wuerttemberg-Hessen, Goethe University , Frankfurt , Germany.
FAU - Kim, Yong-Mi
AU  - Kim YM
AD  - Division of Hematology and Oncology, Department of Pediatrics, Children's 
      Hospital Los Angeles, University of Southern California Keck School of Medicine , 
      Los Angeles, CA , USA.
LA  - eng
GR  - R01 CA172896/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20140523
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC4033044
OTO - NOTNLM
OT  - CD49d
OT  - acute lymphoblastic leukemia
OT  - adhesion
OT  - drug resistance
OT  - integrin alpha4
EDAT- 2014/06/07 06:00
MHDA- 2014/06/07 06:01
PMCR- 2014/01/01
CRDT- 2014/06/07 06:00
PHST- 2014/01/10 00:00 [received]
PHST- 2014/04/22 00:00 [accepted]
PHST- 2014/06/07 06:00 [entrez]
PHST- 2014/06/07 06:00 [pubmed]
PHST- 2014/06/07 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2014.00099 [doi]
PST - epublish
SO  - Front Oncol. 2014 May 23;4:99. doi: 10.3389/fonc.2014.00099. eCollection 2014.