UBTF::ATXN7L3 gene fusion defines novel B cell precursor ALL subtype with CDX2 expression and need for intensified treatment

Oncogenic lesions and molecular subtypes in adults with B‐cell acute lymphoblastic leukemia

“…Soon, three other studies also reported the presence of the same subtype, which was associated with young adults, females, and a high‐risk clinical course. 21 , 22 , 23 CXCR4 ‐activating mutations and PAX5 rearrangements were also characteristics of this subtype. 22 , 23 …”

“…Soon, three other studies also reported the presence of the same subtype, which was associated with young adults, females, and a high-risk clinical course. [21][22][23] CXCR4-activating mutations and PAX5 rearrangements were also characteristics of this subtype. 22,23 CDX2 regulates HOX genes during embryonic hematopoiesis, but it is not expressed in normal adult hematopoietic cells.…”

“…Another interesting finding is that the novel in‐frame fusion transcript, UBTF‐ATXN7L3 , was identified in almost all the cases of this subtype. 21 , 22 , 23 The fusion involving UBTF‐ATXN7L3 results from a 17q21.31 microdeletion between exon 17 of UBTF and exon 1 of ATXN7L3 . UBTF is a nuclear protein that epigenetically regulates rDNA and rRNA transcription.…”

“…22,23 Another interesting finding is that the novel in-frame fusion transcript, UBTF-ATXN7L3, was identified in almost all the cases of this subtype. [21][22][23] The fusion involving UBTF-ATXN7L3 results from a 17q21.31 microdeletion between exon 17 of UBTF and exon 1 of tandem duplication was recurrently identified in pediatric AML, and this alteration may represent a novel subtype-defining lesion. 51 Although the molecular mechanism for B-ALL development of this subtype is poorly understood, defining a close relationship between this group and two universal genomic deletions (13q and 17q deletion) provides us with a hint about a leukemogenic process that may be driven by cooperative effects of the UBTF-ATXN7L3 fusion protein and CDX2 deregulation (Table 1).…”

“… 14 , 19 , 20 More recently, two new high‐risk subtypes involving CDX2 ectopic expression (CDX2/UBTF) and IDH1/2 mutations (IDH1/2‐mut) were identified by some researchers, including us. 21 , 22 , 23 , 24 Notably, most of the recently identified subtypes were more prevalent in AYA/adults than in children. This review describes the recent developments in the molecular pathogenesis and clinical implication of BCR‐ABL1‐negative B‐ALL molecular subtypes in AYA and adults, particularly focusing on three major subtypes, ZNF384‐, DUX4‐, and MEF2D‐rearranged, and two novel subtypes, CDX2/UBTF and IDH1/2‐mut.…”