Quality assessment of autologous haematopoietic blood progenitor cell grafting

This paper showed that infused CD34+ cell dose correlated to platelet but not neutrophil recovery. Interestingly, non-remission status, increasing neutrophil contamination of HPC-A and HPC-A, volumes >500ml were strongly associated with delayed engraftment post-autologous transplantation. In conclusion, considering the recent data published in this issue of the Annals of Hematology, our published and unpublished data, we believe that further variables other than CD34+ cell number play a role in transplant outcome. These findings underline the need of a more extensive quality assessment of autologous PBSCT, taking into account that transplant outcome is not only influenced by graft content but also reflected by other important parameters, such as time in hospital, supportive care with blood transfusions and antibiotic therapy, grade of toxicity and the disease-free survival

Nilotinib interferes with cell cycle, ABC transporters and JAK-STAT signaling pathway in CD34+/lin- cells of patients with chronic phase chronic myeloid leukemia after 12 months of treatment

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyrosine kinase activity of BCR-ABL1 in CML patients. Despite the success of nilotinib treatment in patients with chronic-phase (CP) CML, a population of Philadelphia-positive (Ph+) quiescent stem cells escapes the drug activity and can lead to drug resistance. The molecular mechanism by which these quiescent cells remain insensitive is poorly understood. The aim of this study was to compare the gene expression profiling (GEP) of bone marrow (BM) CD34+/lin- cells from CP-CML patients at diagnosis and after 12 months of nilotinib treatment by microarray, in order to identify gene expression changes and the dysregulation of pathways due to nilotinib action. We selected BM CD34+/lin- cells from 78 CP-CML patients at diagnosis and after 12 months of first-line nilotinib therapy and microarray analysis was performed. GEP bioinformatic analyses identified 2,959 differently expressed probes and functional clustering determined some significantly enriched pathways between diagnosis and 12 months of nilotinib treatment. Among these pathways, we observed the under expression of 26 genes encoding proteins belonging to the cell cycle after 12 months of nilotinib treatment which led to the up-regulation of chromosome replication, cell proliferation, DNA replication, and DNA damage checkpoint at diagnosis. We demonstrated the under expression of the ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCD3 encoding proteins which pumped drugs out of the cells after 12 months of nilotinib. Moreover, GEP data demonstrated the deregulation of genes involved in the JAK-STAT signaling pathway. The down-regulation of JAK2, IL7, STAM, PIK3CA, PTPN11, RAF1, and SOS1 key genes after 12 months of nilotinib could demonstrate the up-regulation of cell cycle, proliferation and differentiation via MAPK and PI3K-AKT signaling pathways at diagnosis

Azacitidine Low-Dose Schedule In Low-Risk Myelodysplastic Syndromes. Preliminary Results of a Multicenter Phase II Study

27nonenoneCarla Filì; Carlo Finelli; Marco Gobbi; Giovanni Martinelli; Ilaria Iacobucci; Emanuela Ottaviani; Lucio Cocco; Matilde Follo; Anna Candoni; Erika Simeone; Maurizio Miglino; Francesco Lauria; Monica Bocchia; Marzia Defina; Cristina Clissa; Francesco Lanza; Antonio Curti; Stefania Paolini; PierAngelo Spedinini; Cristina Skert; Cesare Bergonzi; Michele Malagola; Annalisa Peli; Alessandro Turra; Federica Cattina; Chiara Colombi; Domenico Russo.Carla, Filì; Carlo, Finelli; Marco, Gobbi; Giovanni, Martinelli; Ilaria, Iacobucci; Emanuela, Ottaviani; Lucio, Cocco; Matilde, Follo; Anna, Candoni; Erika, Simeone; Maurizio, Miglino; Francesco, Lauria; Monica, Bocchia; Marzia, Defina; Cristina, Clissa; Francesco, Lanza; Antonio, Curti; Stefania, Paolini; Pierangelo, Spedinini; Cristina, Skert; Cesare, Bergonzi; Malagola, Michele; Annalisa, Peli; Alessandro, Turra; Federica, Cattina; Chiara, Colombi; Russo, Domenic