Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50 % of patients do not respond to AZA and have very poor outcomes. There is thus great interest in identifying predictive biomarkers for AZA responsiveness. We searched for specific genes whose expression level was associated with response status. Using microarrays, we analyzed gene expression patterns in bone marrow CD34 cells in serial samples from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before and during the AZA therapy. At baseline, a comparison of the responders and non-responders showed 52 differentially expressed genes (P < 0.01). Functional annotation of the deregulated genes revealed categories primarily related to ribosomes and pathways associated with proliferation. The expression level of RPL28 correlated with overall survival. We identified altered expression in 167 genes in responders, 26 genes in non-responders with stable disease, and 13 genes in non-responders with disease progression using paired t test of expression levels in patients before and during treatment. Our data indicate that AZA treatment failure is associated with the up-regulation of ribosomal genes/pathways that are likely related to intensive proteosynthesis in proliferative/neoplastic cells of non-responders.
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View Article and Find Full Text PDF[Clinical Analysis of CD4CD8 T-Cell Large Granular Lymphocytic[JP] Leukemia].
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Article Synopsis
- The study investigates the clinical features and treatment of a rare condition called CD4CD8 T-cell large granular lymphocytic leukemia (T-LGLL) through a case report.
- A 70-year-old woman was diagnosed and exhibited symptoms like low platelet counts and myelodysplasia, with blood tests showing an abundance of large granular lymphocytes.
- Treatment involving cyclophosphamide and prednisone led to partial remission, highlighting the unique clinical characteristics of CD4CD8 T-LGLL compared to other forms.
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