The signaling mechanisms responsible for BCR/ABLinduced regulation of Mcl-1 expression in chronic myelogenous leukemia (CML) cells remain unclear. In this study, we show that BCR/ABL could upregulate sphingosine kinase-1 (SPK1) expression via multiple signal pathways, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and Janus kinase 2 (JAK2), leading to increase cellular SPK1 activity in CML cells.
Emerging data demonstrate promising results of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) for the treatment of hematologic malignancies. Data about G-CSF primed PBSC as reliable source of graft with myeloablative conditioning are lacking. We updated the outcomes in 130 adult patients with high-risk hematologic malignancies who received haplo-PBSC transplantation consecutively under busulfan-based conditioning. PBSC were freshly isolated and infused without ex vivo T-cell depletion into the recipients. Myeloid recovery was achieved in 99.2% patients with full donor chimerism. The cumulative incidence of acute grade 3-4 GvHD, overall and extensive chronic GvHD was 14.9%, 38.6% and 16.5%, respectively. The 3-year non-relapse mortality rate was 24.1%. Non-remission prior to transplant was associated with higher incidence of relapse (P=0.006), inferior overall survival (P=0.017) and leukemia-free survival (P=0.024). These data suggest that PBSC is a reliable graft source in haploidentical, unmanipulated transplant settings under myeloablative conditioning in patients with high-risk hematologic malignancies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.