Induced pluripotent stem cells (iPSCs)can be generated by the expression of defined transcription factors not only from normal tissue, but also from malignant cells. Cancer-derived iPSCs are expected to provide a novel experimental opportunity to establish the disease model. We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. Remarkably, the CML-iPSCs were resistant to imatinib although they consistently

We investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit(+) progenitor cells or human CD34(+) peripheral blood hematopoietic progenitors were differentiated in vitro to the erythroid lineage with free iron and/or an iron chelator. Under iron overload, formation of erythroid burst-forming unit colonies and differentiation to mature erythroblasts were significantly suppressed; these effects were canceled by iron chelation with deferoxamine (DFO). Moreover, excessive iron burden promoted apoptosis in immature erythroblasts by elevating intracellular reactive oxygen species (ROS). Interestingly, both DFO and a potent anti-oxidant agent reduced intracellular ROS levels and suppressed apoptosis, thus restoring differentiation to mature erythroblasts. Accordingly, intracellular ROS may represent a new therapeutic target in the treatment of iron overload.

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.

No abstract

Primary anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) is a subtype of primary CNS lymphoma (PCNSL). There are very few comprehensive reports on this extremely rare tumor. Therefore, it is necessary to investigate the clinical features and prognostic factors for primary ALCL of the CNS. We performed a systematic review of the published literature. Past cases were comprehensively searched using PubMed, Cochrane Library, and Web of Science. Clinical information, such as age, sex, anaplastic lymphoma kinase (ALK) status, lesion sites, treatment methods, and survivorship were extracted. Thirty-nine cases with information on ALK status and treatment course were identified. The average observation period was 13 months, and the overall 2-year survival rate was 58%. Univariate analyses showed a statistically significantly better prognosis among patients < 40 years of age (p = 0.039, HR 0.32 (0.11–0.95)) and in relation to ALK positivity (p = 0.010, HR 0.24 (0.08–0.71) and methotrexate treatment (p = 0.003, HR 0.17 (0.05–0.56)). Because of the sparsity of cases, it is necessary to accumulate cases in order to perform more detailed analyses.