API1-MALT1/MLT Is Involved in Mucosa-Associated Lymphoid Tissue Lymphoma With t(11;18)(q21;q21)

There was indeed confusion possible about the nomenclature of theAPI1/API2 genes and, therefore, it is useful to summarize the data. The cloning of API1/API2 was first reported by Rothe et al,1-1 who used the names c-IAP1 and c-IAP2.Liston et al1-2 independently reported the cloning of the same proteins named, respectively, hiap-1 and hiap-2.It should be noted that Hiap-1 corresponds to c-IAP2 andhiap-2 is identical to c-IAP1, which we think is the source of the confusion. The same year, Uren et al1-3 clonedMIHB and MIHC, which are identical to, respectively,c-IAP1 and c-IAP2. The Genome Database always listed the following entries: GDB :9848645 − API1 − alias apoptosis inhibitor 1 − alias MIHB − aliascIAP1 − alias hiap-2 and GDB :9848647 −AP12 − alias apoptosis inhibitor 2 − alias MIHC − alias cIAP2 − alias hiap-1. We thus propose that theAPI2 nomenclature, based on original data and the GDB gene entries, is followed; consequently the t(11;18) generates anAPI2/MLT fusion.

We have obtained from the GDB Gene Nomenclature Committee MLTas the official gene symbol for the gene on 18q21 involved in the t(11;18) found in marginal zone B-cell lymphoma of the MALT type. The t(11;18) breakpoint occurs in different exons of MLT1-4(Baens and Marynen, submitted) and we also showed that differential splicing results in the absence of the GRTDEAVECTE sequence in the MLT protein derived from 3 out of 11 cDNAs we sequenced (Baens and Marynen, submitted). Eight cDNAs contained this exon, as does the EST sequence for clone zq90d12.r1 (GenBank AA214173). Alternative splicing resulting in different protein isoforms is a frequent event and we have no functional data allowing to ‘tentatively choose the cDNA sequence lacking this exon.’ As we were the first to publish the API2/MLT fusion,1-4 theMLT symbol was accepted by the Gene Nomenclature Committee and since there is no reason to assign different gene symbols to different splice variants of the same gene, we propose that Suzuki et al avoid any confusion as happened for API1/API2 and consequently adoptMLT as the gene symbol for the gene involved in the t(11;18).

We performed Northern analyses with the MLT probe on total RNA and detected a major transcript of 3.0 kb. This transcript must correspond to the 3.1 transcript of Suzuki et al. These Northern blots also show a weak band at 4.5 kb. Whether this corresponds to a transcript identical to the longer one seen by Suzuki et al remains to be investigated. Similarly, it remains to be investigated whether the longer open reading frame reported by these authors results from alternative splicing, the use of a different promotor, or from experimental differences, and we agree that this could be relevant with regard to the biology of the MLT protein. In this regard we would like to point out that we presented evidence for the fact that the relevant fusion resulting from the t(11;18) is the one generating anAPI2-MLT mRNA.1-4 In fact, data presented by Akagi et al1-5 seem to support this claim, as in one of their cases the t(11;18) is accompanied by a deletion of 18q sequences, which most probably contains the 5′ part of the MLT gene.