副所院长王建祥带领的研究团队在国际血液学领域的核心期刊《Blood》发表题为"TBLR1 fuses to retinoid acid receptor alpha in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia”的研究论文。
The majority of acute promyelocytic leukemia (APL) cases are characterized by PML-RARα fusion gene. Although PML-RARα fusion gene can be detected in more than 98% of APL cases, RARα is also found to be fused with other partner genes, which are also related to all-trans retinoic acid (ATRA) dependent transcriptional activity and cell differentiation. In this study, we identified a novel RARα fusion gene, TBLR1-RARα (GenBank KF589333), in a rare case of APL with a t(3;17)(q26;q21), t(7;17)(q11.2;q21) complex chromosomal rearrangement. To our knowledge, TBLR1-RARα is the tenth RARα chimeric gene which has been reported up to now. TBLR1-RARα contained the B-F domains of RARα, exhibited a distinct subcellular localization. It could form homodimers and also heterodimers with RXRα. As a result, TBLR1-RARα exhibited diminished transcriptional activity by recruitment of more transcriptional corepressors compared with RARα. In the presence of pharmacological doses of ATRA, TBLR1-RARα could be degraded and its homodimerization was abrogated. Moreover, when treated with ATRA, TBLR1-RARα could mediate the dissociation and degradation of transcriptional corepressors, consequent transactivation of RARα target genes and cell differentiation induction in a dose- and time-dependent manner.