IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
MLL-REARRANGED B LYMPHOBLASTIC LEUKEMIAS SELECTIVELY EXPRESS THE IMMUNOREGULATORY CARBOHYDRATE-BINDING PROTEIN GALECTIN-1
Autor/es:
PRZEMYSLAW JUSZCZYNSKI; SCOTT J. RODIG; JING OUYANG; EVAN O´DONNELL; KUNIHIKO TAKEYAMA; WOJCIECH MLYNARSKI; KATARZYNA MYCKO; TOMASZ SZCZEPANSKI; ANNA GAWORCZYK; ANDREI KRIVTSOV; JOERG FABER; AMIT U. SINHA; GABRIEL A. RABINOVICH; SCOTT A. ARMSTRONG; JEFFERY L. KUTOK; MARGARET A. SHIPP
Revista:
CLINICAL CANCER RESEARCH
Editorial:
AMERICAN ASSOCIATION OF CANCER RESEARCH
Referencias:
Lugar: PHILADELPHIA; Año: 2010
ISSN:
1078-0432
Resumen:
Purpose: Patients with mixed lineage leukemia (MLL)rearranged B-lymphoblastic leukemias (B-ALL)
have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been
identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers
of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein,
Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL.
Experimental Design: Transcriptional profiling of ALL subtypes revealed selective overexpression of
Gal-1 in MLL-rearranged ALLs. For this reason, we analyzed Gal-1 protein expression in MLL-germline
and MLL-rearranged adult and infant pediatric B-ALLs and cell lines by immunoblotting, immunohistochemistry,
and intracellular flow cytometry of viable tumor cell suspensions. Because deregulated gene
expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity
of MLL fusion protein complex, we also analyzed histone H3 lysine 79 (H3K79) dimethylation in the
LGALS1 promoter region using chromatin immunoprecipitation.
Results: Gal-1 transcripts were significantlymore abundant inMLL-rearranged B-ALLs. All 32 primaryMLLrearranged
B-ALLs exhibited abundant Gal-1 immunostaining, regardless of the translocation partner, whereas
only 2 of 81 germline-MLL B-ALLs expressed Gal-1. In addition, Gal-1 was selectively detected in newly diagnosed
MLL-rearranged B-ALLs by intracellular flow cytometry. The LGALS1 promoter H3K79 was significantly
hypermethylated in MLL-rearranged B-ALLs compared with MLL-germline B-ALLs and normal pre-B cells.
Conclusion: In B-ALL, Gal-1 is a highly sensitive and specific biomarker of MLL rearrangement that is
Q2 likely induced by a MLL-dependent epigenetic modification. Clin Cancer Res; 16(7); OF19. ©2010 AACR.