Decreased MYC-associated factor X (MAX) expression is a new potential biomarker for adverse prognosis in anaplastic large cell lymphoma

Takahisa Yamashita,Yuka Tanaka,Morihiro Higashi,Shuji Momose,Jun-Ichi Tamaru,Akiko Adachi,Michihide Tokuhira,Toshiki Watanabe,Masahiro Kizaki

doi:10.1038/s41598-020-67500-w

Abstract

MYC-associated factor X (MAX) is a protein in the basic helix-loop-helix leucine zipper family, which is ubiquitously and constitutively expressed in various normal tissues and tumors. MAX protein mediates various cellular functions such as proliferation, differentiation, and apoptosis through the MYC-MAX protein complex. Recently, it has been reported that MYC regulates the proliferation of anaplastic large cell lymphoma. However, the expression and function of MAX in anaplastic large cell lymphoma remain to be elucidated. We herein investigated MAX expression in anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and found 11 of 37 patients (30%) with ALCL lacked MAX expression, whereas 15 of 15 patients (100%) with PTCL-NOS expressed MAX protein. ALCL patients lacking MAX expression had a significantly inferior prognosis compared with patients having MAX expression. Moreover, patients without MAX expression significantly had histological non-common variants, which were mainly detected in aggressive ALCL cases. Immunohistochemical analysis showed that MAX expression was related to the expression of MYC and cytotoxic molecules. These findings demonstrate that lack of MAX expression is a potential poor prognostic biomarker in ALCL and a candidate marker for differential diagnosis of ALCL and PTCL-NOS.

Highlights

Anaplastic large cell lymphoma (ALCL) is an aggressive mature T-cell lymphoma that usually expresses the lymphocyte activation marker CD30 and often lacks expression of T-cell antigens, such as CD3, CD5, and CD71
We found that decreased MYC-associated factor X (MAX) expression is a potential adverse prognostic factor in anaplastic large cell lymphoma (ALCL) patients
As MAX is an essential molecule for the oncogenic activity of MYC to form a heterodimer with MYC protein, it is conceivable that MAX expression affects MYC-driven oncogenic activity in ALCL

Summary

Introduction

Anaplastic large cell lymphoma (ALCL) is an aggressive mature T-cell lymphoma that usually expresses the lymphocyte activation marker CD30 and often lacks expression of T-cell antigens, such as CD3, CD5, and CD71. MYC can regulate cell proliferation, differentiation, and apoptosis in cooperation with MAX, and this binding to MAX is known to be necessary for MYC transcriptional activities[7]. It has been reported that MYC regulates the proliferation of aggressive mature T-cell lymphomas, ALCL, and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Differential diagnosis of these diseases can be difficult because of their immunophenotypic similarities[8,9,10,11,12]. We determined whether MAX expression can be a candidate biomarker to differentiate between ALCL and PTCL-NOS

Methods

Results

Conclusion