Pre-T-ALL is an important subgroup of ALL with clinical features different from adult T-ALL. Expression of intracytoplasmic CD3 represents the earliest marker for the prethymic phenotype. We studied four consecutive adult patients with this phenotype. Three of the four patients did not respond to the induction chemotherapy with vincristine, daunorubicin, prednisone and asparaginase. They reached a delayed remission only after chemotherapy with cyclophosphamide and cytosine arabinoside. All four patients relapsed 3, 9, 10 and 13 months after diagnosis. One patient died 2 months after relapse, another one 2 months after allogeneic BMT performed in second relapse. We conclude that patients with early T-cell precursor leukemia do not respond adequately to conventional chemotherapy and should be considered as a high-risk subgroup within the T-lineage ALL.
Download full-text PDF |
Source |
---|
J Immunol
October 2014
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125
GATA-3 expression is crucial for T cell development and peaks during commitment to the T cell lineage, midway through the CD4(-)CD8(-) (double-negative [DN]) stages 1-3. We used RNA interference and conditional deletion to reduce GATA-3 protein acutely at specific points during T cell differentiation in vitro. Even moderate GATA-3 reduction killed DN1 cells, delayed progression to the DN2 stage, skewed DN2 gene regulation, and blocked appearance of the DN3 phenotype.
View Article and Find Full Text PDFJ Immunol
June 2014
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095; Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles CA 90095;
Despite the power of model systems to reveal basic immunologic mechanisms, critical differences exist between species that necessitate the direct study of human cells. Illustrating this point is the difference in phenotype between patients with SCID caused by mutations affecting the common γ-chain (γc) cytokine signaling pathway and mice with similar mutations. Although in both species, null mutations in either IL-2RG (which encodes γc), or its direct downstream signaling partner JAK3, result in T and NK cell deficiency, an associated B cell deficiency is seen in mice but not in humans with these genetic defects.
View Article and Find Full Text PDFPLoS One
July 2013
Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, Peking University Health Science Center, Beijing, China.
After a tightly regulated developmental program in the thymus, "mature" single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+) pre-RTEs, a population of CD4(+) SP thymocytes that have acquired the thymus egress capability.
View Article and Find Full Text PDFEur J Immunol
March 2007
Department of Clinical and Biological Sciences (DKBW), Division of Molecular Immunology, Center for Biomedicine, University of Basel, Basel, Switzerland.
The nature and lineage potential, particularly that for B cells, of thymus settling progenitors (TSP) in the adult mouse has been the subject of considerable debate. Lack of B cell potential would suggest pre-thymic, whereas its presence would suggest intra-thymic loss of B cell potential. Using limiting dilution analysis (LDA) in vitro and transfer experiments in vivo, we show that the B cell potential of TSP is critically dependent on mouse age, reaching a maximum of about 1 in 20 cells at birth, decreasing 50-fold in adult mice.
View Article and Find Full Text PDFJ Immunol
August 2003
Department of. Medicine, Stanford University, Stanford, CA 94305, USA.
nu/nu mice fail to develop a thymus and mature T cells due to a defect in the whn gene encoding a transcription factor necessary for terminal epithelial cell differentiation. We investigated whether early T cell progenitor development in the nu/nu bone marrow is also defective. We demonstrated a maturation arrest of nu/nu marrow T cell progenitors associated with a lack of pTalpha gene expression and a failure to give rise to mature T cells in adoptive euthymic hosts.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!