A fluorescent biomarker of the polyamine transport system to select patients with AML for F14512 treatment.
The polyamine transport system (PTS), hyperactive in cancer cells, can constitute a gate to deliver F14512, a novel spermine epipodophyllotoxin conjugate recently selected for clinical development in AML phase I. We investigated in vitro the high antiproliferative effect of F14512 against 13 leukemia cell lines, and demonstrated a statistically significant correlation with the level of PTS activity, using a novel fluorescent marker F96982. This labelling protocol was then adapted for clinical applications for blood, bone marrow and AML samples with CD45 gating. Within the patient samples, the PTS activity varied significantly in AML cells, as compared to normal lymphocytes. In conclusion, the identification of PTS-positive AML with F98982 probe offers new perspectives to select patients prone to respond to F14512.
Annereau
J-P
JP
Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France. jean.philippe.annereau@pierre-fabre.com
Brel
V
V
Dumontet
C
C
Guminski
Y
Y
Imbert
T
T
Broussas
M
M
Vispé
S
S
Bréand
S
S
Guilbaud
N
N
Barret
J-M
JM
Bailly
C
C
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D015317:Biogenic Polyamines / Q000378:metabolism*; D001692:Biological Transport; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010069:Oxadiazoles / Q000378:metabolism*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013096:Spermine / Q000031:analogs & derivatives* / Q000378:metabolism
D018952:Antigens, CD34; D015317:Biogenic Polyamines; C552363:F 96982; C534191:F14512; D005456:Fluorescent Dyes; D010069:Oxadiazoles; D013096:Spermine; D011034:Podophyllotoxin