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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.

Bronchiolitis obliterans (BO) is a severe pulmonary complication of allo-SCT. This study evaluated the incidence of BO in patients undergoing allo-SCT in Hospital Universitário da Universidade Federal do Paraná, risk factors for developing this complication and prognostic factors for those patients who developed this entity. The study included 1286 patients transplanted between 1979 and 2009 who survived for 100 days or more. We diagnosed 53 cases of BO. The cumulative incidence was 2.9% in 1 year and 3.7% in 3 years. Among patients with chronic GVHD, the cumulative incidence at the same intervals was 8.4% and 9.9%, respectively. The median time between transplantation and diagnosis of BO was 260 days (49-3877 days). In the multivariate analysis the risk factors for BO were female donor, older recipients and acute GVHD. The main prognostic factor was the severity of pulmonary impairment. Patients who developed BO earlier than 260 days had a worse prognosis than those who did so later. At least 80% of deaths were directly related to BO.

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