losartan-potassium and Leukemia-Lymphoma--Adult-T-Cell

We report on six cases of unrelated UCB transplant in adult patients with hematological malignancies: three chronic myelocytic leukemias and three acute leukemias. Their median age and body weight were respectively: 28 years (range 15.5-40) and 55.5 kg (range 46-90). The cord blood units were from the New York Blood Center. The median number of nuclear cells provided, evaluated before thawing, was 2.1 x 10(7)/kg (range 1 x 10(7)/kg-4.7 x 10(7)/kg). The degree of HLA disparity was 1/6: two patients, 2/6: three patients, 3/6: one patient. The patients received a pretransplant regimen including total body irradiation. They were given graft-versus-host disease prophylaxis which consisted of cyclosporin A and corticosteroids. They were all given a combination of G-CSF and erythropoietin. The median time of white blood cell and platelet reconstitution were respectively 24 days (range 12-43) and 60 days (range 23-90). All the patients had a full chimerism. A grade I acute GVHD was observed in four patients and two patients do not have any GVHD. No chronic GVHD has been observed yet. Three patients died from toxicity. Three patients are alive and well in complete remission at 2 years, 1 year and 11 months post-graft.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Burkitt Lymphoma; Cyclosporine; Erythropoietin; Female; Fetal Blood; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Immunosuppressive Agents; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male

Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vivo suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and posttranscriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages.

Topics: Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Cell Nucleus; Consensus Sequence; DNA; DNA-Binding Proteins; Erythroblasts; Erythropoietin; Friend murine leukemia virus; Gene Expression; Helix-Loop-Helix Motifs; Humans; Kinetics; Leukemia-Lymphoma, Adult T-Cell; Mice; Mice, Inbred Strains; Molecular Sequence Data; Phosphorylation; Proto-Oncogene Proteins; Restriction Mapping; RNA, Messenger; Signal Transduction; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors; Transcription, Genetic