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

Allogeneic hematopoietic stem cell transplantation for the treatment of BCR-ABL1-negative atypical chronic myeloid leukemia and chronic neutrophil leukemia: A retrospective nationwide study in Japan

Atypical chronic myeloid leukemia(aCML)and chronic neutrophilic leukemia(CNL)are rare BCR-ABL1 fusion gene-negative myeloid neoplasms with a predominance of neutrophils. Since no standard therapeutic strategy currently exists for these diseases,we retrospectively evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aCML and CNL. Data from 14 aCML and 5 CNL patients as their diagnoses were collected using a nationwide survey. Allo-HSCT was performed between 2003 and 2014. Preconditioning regimens included myeloablative (n = 15),reduced-intensity (n = 3), and non-myeloablative (n = 1) regimens. Transplanted stem cells were obtained from HLA-matched related donors (n = 5) and alternative donors (n = 14). Neutrophil engraftment was successfully achieved in 17 patients. One-year overall survival rates (OS) were 54.4% (95% confidence interval [CI], 24.8 to 76.7%) and 40.0% (95% CI, 5.2 to 75.3%) in patients with aCML and CNL, respectively. Among aCML patients, 1-year OS were 76.2% (95% CI, 33.2 to 93.5%) and 20.0% (95% CI, 0.8 to 58.2%) in patients with <5% myeloblasts (n = 9) and ?5% myeloblasts (n = 5) in peripheral blood before allo-HSCT, respectively. These results suggest that allo-HSCT achieves long-term survival in patients with aCML and CNL. Better pre-transplant management is required to improve the outcomes of aCML patients with ?5% blasts in peripheral blood