MLL-rearranged B Lymphoblastic Leukemias Selectively Express the Immunoregulatory Carbohydrate-binding Protein Galectin-1

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2010 Mar 25

PMID 20332322

Citations 16

Authors

Przemyslaw Juszczynski

Scott J Rodig

Jing Ouyang

Evan ODonnell

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

Affiliations

Soon will be listed here.

Abstract

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 the 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 significantly more abundant in MLL-rearranged B-ALLs. All 32 primary MLL-rearranged 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 likely induced by a MLL-dependent epigenetic modification.

Citing Articles

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Kapetanakis N, Busson P Front Immunol. 2023; 14:1145268.

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Galectin-1 and Galectin-3 in B-Cell Precursor Acute Lymphoblastic Leukemia.

Fei F, Zhang M, Tarighat S, Joo E, Yang L, Heisterkamp N Int J Mol Sci. 2022; 23(22).

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Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy?.

Shi Y, Tang D, Li X, Xie X, Ye Y, Wang L Front Oncol. 2022; 12:889034.

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