PMID- 33255664
OWN - NLM
STAT- MEDLINE
DCOM- 20210305
LR  - 20210305
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 23
DP  - 2020 Nov 25
TI  - Microfluidic-Based Detection of AML-Specific Biomarkers Using the Example of 
      Promyelocyte Leukemia.
LID - 10.3390/ijms21238942 [doi]
LID - 8942
AB  - A microfluidic assay for the detection of promyelocytic leukemia (PML)-retinoic 
      acid receptor alpha (RARalpha) fusion protein was developed. This microfluidic-based 
      system can be used for rapid personalized differential diagnosis of acute 
      promyelocyte leukemia (APL) with the aim of early initiation of individualized 
      therapy. The fusion protein PML-RARalpha occurs in 95% of acute promyelocytic 
      leukemia cases and is considered as diagnostically relevant. The fusion protein 
      is formed as a result of translocation t(15,17) and is detected in the laboratory 
      by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase 
      chain reaction (RT-PCR). Diagnostic methods require many laboratory steps with 
      specialized staff. The developed microfluidic assay includes a sandwich 
      enzyme-linked immunosorbent assay (ELISA) system for PML-RARalpha on surface of 
      magnetic microparticles in a microfluidic chip. A rapid detection of PML-RARalpha in 
      cell lysates is achieved in less than one hour. A biotinylated PML-antibody on 
      the surface of magnetic streptavidin coated microparticles is used as capture 
      antibody. The bound translocation product is detected by a RARalpha antibody 
      conjugated with horseradish peroxidase and the substrate QuantaRed. The analysis 
      is performed in microfluidic channels which involves automated liquid processing 
      with stringent washing and short incubation times. The results of the developed 
      assay show that cell lysates of PML-RARalpha-positive cells (NB-4) can be clearly 
      distinguished from PML-RARalpha-negative cells (HL-60, MV4-11).
FAU - Emde, Benedikt
AU  - Emde B
AD  - Department Hamm 1, Hamm-Lippstadt University of Applied Science, 59063 Hamm, 
      Germany.
FAU - Kreher, Heike
AU  - Kreher H
AD  - Micronit GmbH, 44263 Dortmund, Germany.
FAU - Baumer, Nicole
AU  - Baumer N
AD  - Department of Medicine A, Hematology and Oncology, University of Muenster, 48149 
      Muenster, Germany.
FAU - Baumer, Sebastian
AU  - Baumer S
AD  - Department of Medicine A, Hematology and Oncology, University of Muenster, 48149 
      Muenster, Germany.
FAU - Bouwes, Dominique
AU  - Bouwes D
AD  - Micronit GmbH, 44263 Dortmund, Germany.
FAU - Tickenbrock, Lara
AU  - Tickenbrock L
AD  - Department Hamm 1, Hamm-Lippstadt University of Applied Science, 59063 Hamm, 
      Germany.
LA  - eng
GR  - ZF4147102SB6/Research funded by "Zentrales Innovationsprogramm Mittelstand (ZIM)" 
      by the "Bundesministerium fur Wirtschaft und Energie"/
PT  - Journal Article
DEP - 20201125
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Promyelocytic Leukemia Protein)
RN  - 0 (RARA protein, human)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein)
RN  - 143220-95-5 (PML protein, human)
SB  - IM
MH  - Biomarkers, Tumor/genetics/isolation & purification
MH  - Granulocyte Precursor Cells/metabolism/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Leukemia, Promyelocytic, Acute/*diagnosis/genetics/pathology
MH  - Microfluidics/methods
MH  - Oncogene Proteins, Fusion/*genetics/isolation & purification
MH  - Precision Medicine
MH  - Promyelocytic Leukemia Protein/*genetics
MH  - Retinoic Acid Receptor alpha/*genetics
MH  - Translocation, Genetic/genetics
PMC - PMC7728129
OTO - NOTNLM
OT  - acute myeloid leukemia
OT  - bio-microfluidics
OT  - lab-on-a-chip
OT  - magnetic bead-based immunoassay
OT  - personalized diagnostics and medicine
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/12/02 06:00
MHDA- 2021/03/06 06:00
PMCR- 2020/12/01
CRDT- 2020/12/01 01:09
PHST- 2020/11/19 00:00 [received]
PHST- 2020/11/23 00:00 [accepted]
PHST- 2020/12/01 01:09 [entrez]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/03/06 06:00 [medline]
PHST- 2020/12/01 00:00 [pmc-release]
AID - ijms21238942 [pii]
AID - ijms-21-08942 [pii]
AID - 10.3390/ijms21238942 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Nov 25;21(23):8942. doi: 10.3390/ijms21238942.