Identification of a molecular signature predictive of sensitivity to differentiation induction in acute myeloid leukemia.
Acute myeloid leukemia (AML) blasts are immature committed myeloid cells unable to spontaneously undergo terminal maturation, and characterized by heterogeneous sensitivity to natural differentiation inducers. Here, we show a molecular signature predicting the resistance or sensitivity of six myeloid cell lines to differentiation induced in vitro with retinoic acid or vitamin D. The identified signature was further validated by TaqMan assay for the prediction of response to an in vitro differentiation assay performed on 28 freshly isolated AML blast populations. The TaqMan assay successfully predicts the in vitro resistance or responsiveness of AML blasts to differentiation inducers. Furthermore, performing a meta-analysis of publicly available microarray data sets, we also show the accuracy of our prediction on known phenotypes and suggest that our signature could become useful for the identification of patients eligible for new therapeutic strategies.
Tagliafico
E
E
Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena e Reggio Emilia, Modena, Italy.
Tenedini
E
E
Manfredini
R
R
Grande
A
A
Ferrari
F
F
Roncaglia
E
E
Bicciato
S
S
Zini
R
R
Salati
S
S
Bianchi
E
E
Gemelli
C
C
Montanari
M
M
Vignudelli
T
T
Zanocco-Marani
T
T
Parenti
S
S
Paolucci
P
P
Martinelli
G
G
Piccaluga
P P
PP
Baccarani
M
M
Specchia
G
G
Torelli
U
U
Ferrari
S
S
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D016208:Databases, Factual; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015201:Meta-Analysis as Topic; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology
D000970:Antineoplastic Agents; D014815:Vitamins; D014807:Vitamin D; D014212:Tretinoin