14q32/miRNA clusters loss of heterozygosity in acute lymphoblastic leukemia is associated with up-regulation of BCL11a.
This study evaluated the loss and expression level of miRNAs 14q32 clusters in acute lymphoblastic leukemia (ALL) patients with cryptic deletions at 14q32 chromosomal band to investigate their involvement in this disease. We demonstrate that a subset of ALL cases bearing 14q32 LOH showed a down-regulation of miRNA 14q32 clusters, which is directly linked to the submicroscopic chromosomal deletion. As a consequence of miRNAs deregulation we reported an inverse correlation with the expression of their target BCL11a, a transcription factor involved in lymphoid differentiation. These results suggest that 14q32/miRNA clusters LOH may be another mechanism involved in lymphoid B cell transformation and differentiation and therefore, could be used as a diagnostic marker and therapeutic target in subsets of ALL.
Agueli
Cecilia
C
Divisione di ematologia con UTMO, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
Cammarata
Giuseppe
G
Salemi
Domenico
D
Dagnino
Lea
L
Nicoletti
Roberta
R
La Rosa
Maria
M
Messana
Francesca
F
Marfia
Anna
A
Bica
Maria Grazia
MG
Coniglio
Maria Luisa
ML
Pagano
Maria
M
Fabbiano
Francesco
F
Santoro
Alessandra
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics* / Q000648:ultrastructure; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins; D017384:Sequence Deletion; D015854:Up-Regulation; D055815:Young Adult
C486563:BCL11A protein, human; D002352:Carrier Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins