Luceno-Araujo et al use assays of mutations associated with myeloid malignancy to propose an integrative prognostic score for acute promyelocytic leukemia (ISAPL) in patients treated with all-trans retinoic acid and anthracycline-based therapy. They demonstrate that the ISAPL is superior for predicting outcomes and identifying patients who may benefit from alternative therapies to maximize their chance of a cure.

The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2high transcript levels were associated with cell cycle arrest, while SLIT2low APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92–0.97; p < 0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated.

non-t cell activation linker (ntAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. in acute promyelocytic leukemia (ApL), ntAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of ntAL were associated with increased all-trans retinoic acid (AtRA)induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, ntAL-knockdown (ntAL-KD) in ApL cell lines led to activation of Ras, inhibition of Akt/ mtoR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (noD scid gamma) nSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with AtRA and anthracyclines, revealed that

SummaryThe Latin Americas and Caribbean are regions where social exclusion and inequality persist as the main obstacles to human development and improvement of health conditions, despite economic growth and social development. These countries need to establish international collaborations with the goal of improving health conditions. In this scenario Acute Promyelocytic Leukaemia (APL), a disease with a high cure rate in developed countries and high prevalence in young patients, offers an ideal opportunity to implement measures with educational and cooperative scope. We discuss the experience of Latin America and the Caribbean through a common network, the International Consortium on Acute Promyelocytic Leukaemia (IC-APL).