Jun Nomiyama

Donor cell-derived acute myeloid leukemia after unrelated umbilical cord blood transplantation

Donor cell-derived acute myeloid leukemia after unrelated umbilical cord blood transplantation

Autografting followed by a reduced-intensity conditioning unrelated donor cord blood transplantation for a patient with refractory multiple myeloma: successful engraftment with minimal toxicity

Abstract:  We report on a 59‐yr‐old man with recurrent multiple myeloma. To reduce treatment‐related mortality, while retaining the cytoreductive effects of high‐dose chemotherapy, as well as graft vs. myeloma effect, we used a reduced‐intensity conditioning umbilical cord blood (CB) transplantation following high‐dose chemotherapy with autologous stem cell transplantation support. This patient was engrafted rapidly and extramedullary toxicities were acceptable. Although he had local recurrence in the right calf on day +130 after the CB transplantation, the tumor was successfully treated with radiation therapy, and he is alive and well at present (day +480).

Recurrent extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation in a patient with the chromosomal abnormality t(8;21) and CD56-positivity

Isolated extramedullary (EM) relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare. Predisposing factors include CD56 expression and the chromosomal abnormality t(8;21). We describe an AML patient showing the chromosomal abnormality t(8;21) and CD56 expression who experienced a unique EM relapse after allo-HSCT. Approximately 10 months after allo-HSCT, he experienced relapse involving the femur and lumbar vertebrae and, subsequently, an EM relapse of the stomach. Although we administered only local radiotherapy and not systemic chemotherapy, he showed no bone marrow relapse on long-term follow-up after achieving complete hematological remission. These findings suggest that the graft-versus-leukemia effect may preferentially maintain marrow remission rather than prevent EM relapse. In addition, our findings show that extended survival is possible after EM relapse following allo-HSCT in patients with marrow hematopoiesis of donor origin, and that augmentation of the graft-versus-leukemia effect may be useful.

Overexpression of dominant negative mutant hepatocyte nuclear factor (HNF)-1α inhibits arginine-induced insulin secretion in MIN6 cells

Aims/hypothesis. To explain the mechanisms whereby mutations in the HNF-1α gene cause insulin secretory defects. Methods. A truncated mutant HNF-1α (HNF-1α288 t) was overexpressed in hepatoma cells (HepG2) and murine insulinoma cells (MIN6) using a recombinant adenovirus system and expression of the HNF-1α target genes and insulin secretion were examined. Results. Expression of phenylalanine hydroxylase and α1-antitrypsin genes, the target genes of HNF-1α, was suppressed in HepG2 cells by overexpression of HNF-1α288 t. In MIN6 cells, overexpression of HNF-1α288 t did not change insulin secretion stimulated by glucose (5 mmol/l and 25 mmol/l) or leucine (20 mmol/l). Potentiation of insulin secretion by arginine (20 mmol/l, in the presence of 5 mmol/l or 25 mmol/l glucose) was, however, reduced (p < 0.0001 and p = 0.027, respectively). Similarly reduced responses were observed when stimulated with homoarginine. Expression of the cationic amino acid transporter-2 was not reduced and insulin secretory response to membrane depolarization by 50 mmol/l KCl was intact. Conclusion/interpretation. The HNF-1α288 t, which is structurally similar to the mutant HNF-1α expressed from the common MODY3 allele, P291fsinsC, exerts a dominant negative effect. Suppression of HNF-1α in MIN6 cells severely impaired potentiation of insulin secretion by arginine, whereas glucose-stimulated and leucine-stimulated insulin secretion was intact. Our findings delineate the complex nature of beta-cell failure in patients with MODY3. This cell model will be useful for further investigation of the mechanism of insulin secretory defects in these patients. [Diabetologia (1999) 42: 887–891]