ABSTRACT
Peripheral blood stem cells (PBSC) became the main source of cells for autologous transplantation. Alterations in the expression of adhesion molecules are essential in the CD34+ cells mobilization process. These molecules are involved in the interaction between hematopoietic and stromal cells and they have been disclosed as a considerable factor to the trafficking and homing of the CD34+ progenitor cells. This is a non-randomized PBSC mobilization study designed to evaluate the influence and behavior of FL and SDF-1 and their receptors in two different moments, prior and after HPCs mobilization, with the yield of CD34+ cells collected by apheresis. There was higher concentration of FL and lower of SDF-1 plasma level at post than pre PBSC mobilization (p=0.001 and p=0.012, respectively) regarding all individuals searched, but without any correlation with a good yield of CD34+ cells. However, CXCR4 expressions on the CD34+ cells from bone marrow aspirates (BMA), at pre and post mobilization showed a difference statistical significant for those individuals with good yield of CD34+ cells (p=0,036), but not achieved for poor yield (p=0,156). There was a higher expression of CXCR4 in steady-state for the successfully individuals than for those unsuccessfully (529.84+/-54.68 and 496.31+/-97.51, respectively). In conclusion, we confirmed the important role of CXCR4/SDF-1 axis in the process of PBSC mobilization.
Subject(s)
Chemokine CXCL12/blood , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells/metabolism , Receptors, CXCR4/metabolism , fms-Like Tyrosine Kinase 3/blood , Adult , Antigens, CD34 , Bone Marrow Examination , Down-Regulation , Female , Humans , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Receptors, CXCR4/blood , Young AdultABSTRACT
Although the zeta-associated protein of 70 kDa (ZAP-70) is overexpressed in patients with chronic lymphocytic leukemia (CLL) displaying unmutated IGVH genes and poor prognosis, a previous microarray study from our group identified overexpression of LPL and ADAM29 genes among unmutated and mutated CLL, respectively. To assess the prognostic value of these genes, we quantified their expression by real-time quantitative polymerase chain reaction (PCR) in a cohort of 127 patients with CLL and correlated this with clinical outcome, IGVH mutational status, and ZAP-70 protein expression. IGVH mutational status, ZAP-70, and the LPL and ADAM29 mRNA ratios (L/A ratio) were predictive of event-free survival for the whole cohort and for patients with stage A disease. In patients in stage B and C, the L/A ratio was an independent prognostic factor, whereas ZAP-70 did not predict survival. Simultaneous usage of the L/A ratio and ZAP-70 expression allowed an almost perfect (99%) assessment of the IGVH status in the 80% of patients with concordant results (L/A+, ZAP-70+ or L/A-, ZAP-70-). LPL and ADAM29 gene expression could also be determined by a simple competitive multiplex reverse transcription PCR assay. Overall, quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lipoprotein Lipase/genetics , Metalloendopeptidases/genetics , ADAM Proteins , Base Sequence , Biomarkers, Tumor/genetics , Case-Control Studies , DNA, Complementary/genetics , DNA, Neoplasm/genetics , Female , Gene Expression , Genes, Immunoglobulin , Humans , Immunoglobulin Heavy Chains/genetics , Male , Middle Aged , Mutation , Prognosis , Protein-Tyrosine Kinases/genetics , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , ZAP-70 Protein-Tyrosine KinaseABSTRACT
CONTEXTO: O prognóstico da anemia aplástica grave melhorou com o advento do transplante de medula óssea e do tratamento imunossupressor com globulina antitimocitária. Em contraste com o sucesso destes protocolos, os estudos com seguimento a longo prazo mostraram a ocorrência de doenças clonais, tais como: hemoglobinúria paroxística noturna, síndrome mielodisplásica e leucemia aguda. RELATO DE CASO: Nós relatamos o primeiro caso descrito no Brasil de um paciente com anemia aplástica que evoluiu para síndrome mielodisplásica e leucemia mielóide aguda associada a presença de hemoglobina H e aumento da hemoglobina fetal.
Subject(s)
Humans , Male , Adult , Anemia, Aplastic/complications , Hemoglobin H , Leukemia, Myeloid/etiology , Acute Disease , Anemia, Aplastic/drug therapy , Anemia, Aplastic/surgery , Antilymphocyte Serum/administration & dosage , Antilymphocyte Serum/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Transplantation/adverse effects , Fatal Outcome , Globins/biosynthesis , Leukemia, Myeloid/drug therapy , Myelodysplastic Syndromes/complications , Time FactorsABSTRACT
CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.