A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types

Species-Specific Therapy of Acute Lymphoid Leukemia

Forty years ago, Farber and associates described temporary remissions of acute leukemia in children produced by folic acid antagonists [13]. This ignited the hope that this most frequent and always fatal childhood cancer might be curable by drugs. Twenty years ago, Aur and as-sociates completed accession of patients to total therapy study V, the first treat-ment protocol to result in 50 % cure of acute lymphoid leukemia (ALL) [3]. Their results stand 20 years later (Fig. 1), and have been reproduced throughout the world in many thousands of children [6]. More important, recent national vital statistics of the United States and the United Kingdom indicate a 50 % reduc-tion in childhood leukemia mortality [4, 29]. Further, the cured children generally enjoy a normal life-style without need for medication. In the past 20 years, efforts have been directed at improving the cure rate of ALL while simplifying curative treat-ment, reducing its side effects, and im-proving its availability and accessibility. In a Stohlman Lecture at Wilsede 10 years ago the following statement was made [32]:- The most significant opportunity for improving the treatment of acute lymphoid leukemia in the past five years has been its biological and clini-cal classification by immunological cell surface markers. This allows spe-cies identification of the leukemia cells, the first step toward developing specific cytocidal or cytostatic therapy