Interferon alpha is an effective therapy for congenital dyserythropoietic anaemia type I.

The efficacy of interferon-alpha (IFN) was reported in three patients with congenital dyserythropoietic anaemia (CDA) type I. We describe two additional cases treated with IFN, which normalized the haemoglobin level in both patients with a dramatic decrease in the size of the spleen in one. Haemoglobin remained stable more than 6 months after discontinuation of treatment. IFN induced more than 50% decrease in the number of BFU-E in both patients' bone marrow cultures, suggesting an indirect effect of IFN on erythropoiesis in vivo. We conclude that a trial of IFN therapy should be considered in patients with CDA type I.

Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells.

Human T-cell lymphotropic virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL). ATL is an aggressive proliferation of mature activated T cells associated with a poor prognosis. The combination of the antiviral agents, zidovudine (AZT) and interferon (IFN), is a potent treatment of ATL. Recently, arsenic trioxide (As) was shown to be an effective treatment of acute promyelocytic leukemia (APL). We have tested the effects of the combination of As and IFN on cell proliferation, cell cycle phases distribution, and apoptosis in ATL-derived or control T-cell lines. A high synergistic effect between IFN and As was observed in ATL-derived cell lines in comparison to the control cell lines, with a dramatic inhibition of cell proliferation, G1 arrest, and induction of apoptosis. Similar results were obtained with fresh leukemia cells derived from an ATL patient. Although the mechanisms involved are unclear, these results could provide a rational basis for combined As and IFN treatments in ATL.

Thiamine-responsive myelodysplasia.

The triad of thiamine-responsive anaemia, diabetes mellitus and deafness has been reported in 15 patients with macrocytic anaemia, sometimes associated with moderate thrombocytopenia. The bone marrow aspirate usually shows megaloblastic changes and ringed sideroblasts. However, tri-lineage myelodysplasia has never been reported. We describe two patients who presented with diabetes, deafness and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of tri-lineage myelodysplasia. These findings suggest that thiamine may have a role in the regulation of haemopoiesis at the stem cell level. We propose the term 'thiamine-responsive myelodysplasia' rather than that of thiamine-responsive anaemia.

mdm-2 oncoprotein expression associated with deletion of the long arm of chromosome 12 in a case of mantle cell lymphoma with blastoid transformation [corrected].

We report a unique case of mantle cell lymphoma in blastoid transformation associated with deletion of the long arm of chromosome 12 and with 90 kDa mdm-2 protein overexpression. Neither the mantle cells nor their blastoid counterparts expressed p53 gene product by immunohistochemical analysis. This seems to be the first reported case of this subtype of lymphoma associated with these specific cytogenetic and molecular genetic abnormalities.

Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors.

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)