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.

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