Molecular characterization and clinical impact of t(11;15)(q23;q14-15) MLL-CASC5 rearrangement
摘要
The identification of novel translocation partner genes involved in MLL rearrangements increases the chances of identifying novel possibilities for a targeted, molecular therapy. Concerted efforts by many research groups in collaboration with the Diagnostic Center of Acute Leukemia (DCAL) at Frankfurt University have made it possible to establish the MLL recombinome database.1 From these studies it became clear that just a few translocation partner genes account for over 90% of leukemia patients, and that the vast majority of MLL partner genes is relatively infrequent. Nevertheless, these rare but recurrent MLL rearrangements are also of importance, and, therefore, collaborative efforts are required to analyze their function(s) and impact on clinical outcome. In this regard, we recently reported MLL-TET1 rearrangements, which belong to a category of rare MLL rearrangements.2 Here we present comprehensive analyses of patients with MLL-CASC5 rearrangements resulting from t(11;15)(q23;q14–15) chromosomal translocations of which only 13 cases have been reported so far.3–9 The CASC5 (alias AF15q14) gene is located at chromosome 15q14, consists of 27 exons, and spans a genomic region of 70.32 kb. The encoded CASC5 protein is known to be associated with cell growth suppression and/or maturation enhancement and thus its disruption could be a key factor for leukemogenesis.4 To date, 3 cases have been molecularly confirmed as MLL-CASC5 positive leukemia (MLL-CASC5+).3,4 However, little is known about the common features of MLL-CASC5+ leukemia both in terms of detailed molecular data and clinical aspects. In order to gain further insights into this rare MLL fusion, we have collected t(11;15)(q23;q14–15)/MLL-CASC5+ leukemia cases and describe their clinical features (Table 1). By analyzing the molecular and clinical characteristics of these patients along with previously reported t(11;15)(q23;q14–15) cases, we aimed to unravel the distinct features of this cytogenetically de