Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens

We report the identification of two novel minor histocompatibility antigens (mHAgs), encoded by two separate single nucleotide polymorphisms on a single gene, BCL2A1, and restricted by human histocompatibility leukocyte antigen (HLA)-A*2402 (the most common HLA-A allele in Japanese) and B*4403, respectively. Two cytotoxic T lymphocyte (CTL) clones specific for these mHAgs were first isolated from two distinct recipients after hematopoietic cell transplantation. Both clones lyse only normal and malignant cells within the hematopoietic lineage. To localize the gene encoding the mHAgs, two-point linkage analysis was performed on the CTL lytic patterns of restricting HLA-transfected B lymphoblastoid cell lines obtained from Centre d'Etude du Polymorphisme Humain. Both CTL clones showed a completely identical lytic pattern for 4 pedigrees and the gene was localized within a 3.6-cM interval of 15q24.3–25.1 region that encodes at least 46 genes. Of those, only BCL2A1 has been reported to be expressed in hematopoietic cells and possess three nonsynonymous nucleotide changes. Minigene transfection and epitope reconstitution assays with synthetic peptides identified both HLA-A*2402– and B*4403-restricted mHAg epitopes to be encoded by distinct polymorphisms within BCL2A1

S-1 monotherapy for previously treated non-small cell lung cancer: A retrospective analysis by age and histopathological type

S-1, an oral fluoropyrimidine derivative, has been approved for the treatment of non-small cell lung cancer (NSCLC) in Japan. In the present study, the efficacy and safety of S-1 monotherapy for elderly patients with previously treated NSCLC were retrospectively evaluated, and the efficacy of S-1 monotherapy was compared by histopathological type. This retrospective study included 54 patients with advanced or recurrent NSCLC who had received S-1 monotherapy following the failure of previous chemotherapy regimens at our institutes. Patient outcomes were compared based on their age and histopathological type. S-1 was administered orally, twice daily, while the duration and interval were modified according to the medical condition of each patient. The default delivery schedule, the mean number of S-1 cycles, did not differ significantly between the two age groups (<70 and ≥70 years). The rate of therapy discontinuation, schedule modification or dose reduction due to intolerable toxicities or patient refusal was relatively frequent in the older group (40.7 and 55.6% for ages <70 and ≥70 years, respectively; p=0.414), and the incidence of grade 3 anemia was relatively high in the older group (3.7 and 18.5%, respectively; p=0.192). The response rates (13.0 and 4.8%, respectively; p=0.609) and disease control rates (39.1 and 33.3%, respectively; p=0.761) did not differ significantly between the two age groups. According to histopathological type, the disease control rate was significantly higher in adenocarcinoma (57.9%) compared to non-adenocarcinoma (20.0%, p=0.013). Thus, S-1 monotherapy may be equally effective and tolerated in patients <70 years and those ≥70 years. Additionally, adenocarcinoma may have a higher disease control rate than non-adenocarcinoma