Chemosensitivity is differentially regulated by the SDF-1/CXCR4 and SDF-1/CXCR7 axes in acute lymphoblastic leukemia with MLL gene rearrangements.
Leuk Res
; 75: 36-44, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30453100
ABSTRACT
Although recent advances in chemotherapy have markedly improved outcome of acute lymphoblastic leukemia (ALL), infantile ALL with MLL gene rearrangements (MLL+ALL) is refractory to chemotherapy. We have shown that specific cytokines FLT3 ligand and TGFß1 both of which are produced from bone marrow stromal cells synergistically induced MLL+ALL cells into chemo-resistant quiescence, and that treatment of MLL+ALL cells with inhibitors against FLT3 and/or TGFß1 receptor partially but significantly converts them toward chemo-sensitive. In the present study, we showed that MLL+ALL cells expressed CXCR4 and CXCR7, both receptors for the same chemokine stromal cell derived factor-1 (SDF-1), but their biological events were differentially regulated by the SDF-1/CXCR4 and SDF-1/CXCR7 axes and particularly exerted an opposite effect for determining chemo-sensitivity of MLL+ALL cells; enhancement via the SDF-1/CXCR4 axis vs. suppression via the SDF-1/CXCR7 axis. Because cytosine-arabinoside-induced apoptosis of MLL+ALL cells was inhibited by pretreatment with the CXCR4 inhibitor but rather accelerated by pretreatment with the CXCR7 inhibitor, an application of the CXCR7 inhibitor may become a good treatment option in future for MLL+ALL patients. MLL+ALL has a unique gene profile distinguishable from other types of ALL and AML, and should be investigated separately in responses to biological active agents including chemokine inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
N-Metiltransferasa de Histona-Lisina
/
Resistencia a Antineoplásicos
/
Proteína de la Leucemia Mieloide-Linfoide
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Límite:
Humans
Idioma:
En
Revista:
Leuk Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón