Low BACH2 Expression Predicts Adverse Outcome in Chronic Lymphocytic Leukaemia

Peixun Zhou, Vikki Rand, Carmela Ciardullo, Katarzyna Szoltysek, Elaine Willmore, Amir Enshaei, Andy Hall, Christine J Harrison, Meera Soundararajan, Jeyanthy Eswaran, Monika Pietrowska, Lukasz Marczak, Anna Walaszczyk, Jia Yee Ho, Scott Marshall

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with a highly variable clinical outcome. There are well‐established CLL prognostic biomarkers that have transformed treatment and improved the understanding of CLL biology. Here, we have studied the clinical significance of two crucial B cell regulators, BACH2 (BTB and CNC homology 1, basic leucine zipper transcription factor 2) and BCL6 (B‐cell CLL/lymphoma 6), in a cohort of 102 CLL patients and determined the protein interaction networks that they participate in using MEC‐1 CLL cells. We observed that CLL patients expressing low levels of BCL6 and BACH2 RNA had significantly shorter overall survival (OS) than high BCL6‐ and BACH2‐expressing cases. Notably, their low expression specifically decreased the OS of immunoglobulin heavy chain variable region‐mutated (IGHV‐M) CLL patients, as well as those with 11q and 13q deletions. Similar to the RNA data, a low BACH2 protein expression was associated with a significantly shorter OS than a high expression. There was no direct interaction observed between BACH2 and BCL6 in MEC‐1 CLL cells, but they shared protein networks that included fifty different proteins. Interestingly, a prognostic index (PI) model that we generated, using integrative risk score values of BACH2 RNA expression, age, and 17p deletion status, predicted patient outcomes in our cohort. Taken together, these data have shown for the first time a possible prognostic role for BACH2 in CLL and have revealed protein interaction networks shared by BCL6 and BACH2, indicating a significant role for BACH2 and BCL6 in key cellular processes, including ubiquitination mediated B‐cell receptor functions, nucleic acid metabolism, protein degradation, and homeostasis in CLL biology.

Original languageEnglish
Article number23
JournalCancers
Volume14
Issue number1
DOIs
Publication statusPublished - 21 Dec 2021

Bibliographical note

Funding Information:
Funding: This research was funded by Blood Cancer UK (previously known as Bloodwise) and JGW Patterson Foundation, Jeyanthy Eswaran was funded by the Marie Curie International Incoming Fellowship. Vikki Rand was supported by the Bloodwise Bennett Fellowship #12005 and Peixun Zhou was supported by Bright Red.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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