Monocytic differentiation induced by side-chain modified analogs of vitamin D in ex vivo cells from patients with acute myeloid leukemia.
The differentiation-inducing potential of side-chain modified analogs of vitamins D, compared to the reference compound, 1,25-dihydroxyvitamin D3, was studied in blast cells from patients with acute myeloid leukemia and in cell lines. Analogs PRI-1906 and PRI-1907 showed increased cell-differentiation activities, PRI-1907 even at a very low concentration. Our study revealed a high variability of individual patients' blasts in their susceptibility to vitamin D analogs. The blasts of the patients with normal karyotype and with mutated NPM1 reacted to analogs with stronger differentiation than the blasts of the remaining patients, while the blasts with mutated FLT3 receptor reacted with weaker differentiation than the remaining blasts.
Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland.
Hanna
H
Baurska
Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Pasteura 4, 50-367 Wrocław, Poland.
Marek
M
Kiełbiński
Institute of Applied Mathematics and Mechanics, University of Warsaw, Krakowskie Przedmieście 26/28, Warszawa, Poland.
Przemysław
P
Biecek
Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, Skłodowska-Curie 9, 85-094 Bydgoszcz, Poland.
Olga
O
Haus
Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Pasteura 4, 50-367 Wrocław, Poland.
Bożena
B
Jaźwiec
Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warszawa, Poland.
Andrzej
A
Kutner
Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland. Electronic address: ema@cs.uni.wroc.pl.
Ewa
E
Marcinkowska
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D009154:Mutation; D000090243:Nucleophosmin; D014807:Vitamin D / Q000031:analogs & derivatives*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
C000716967:NPM1 protein, human; D000090243:Nucleophosmin; D014807:Vitamin D; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
1 ;25-dihydroxyvitamin D(3); Acute myeloid leukemia; Blasts; Differentiation; Flow cytometry; Personalized anticancer therapy; Statistical analysis; Vitamin D analogs