Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype.

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Summary Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX‐IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX‐ or DFX‐related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion‐independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Key Points We present real-world data on all ruxolitinib-treated myelofibrosis patients in a 10-million-resident region, with a follow-up of 2 years. We found no evidence of an increased risk of developing lymphomas.

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Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1), is approved for the treatment of patients with ALK-positive (ALK+) or ROS1-positive (ROS1+) advanced non-smallcell lung cancer (NSCLC). The ALK rearrangements are also implicated in anaplastic large-cell lymphoma (ALCL), which is characterized by

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IntroductionThe Coronavirus disease 2019 (COVID-19) pandemic and the resulting social distancing, determined a reduction in access to care and limitations of individual freedom, with a consequent strong impact on quality of life (QoL), anxiety levels and medical management of onco-hematological people. In particular, in the case of patients with chronic myeloproliferative neoplasm (MPN), concern about SARS-CoV-2 infection added to the burden of symptoms (BS) which already weights on the QoL of these patients. We designed a cross-sectional survey in order to investigate the impact of the COVID-19 pandemic on status of anxiety, BS and QoL in MPN patients.MethodsWe analyzed the anxiety levels using the Zung Self-Rating Anxiety Scale (SAS); BS modifications were studied using the 18 items of the Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF].Results132 people answered to the survey: 27 (20.4%) patients achieved a moderate to marked anxiety index value: this group described a greater worsening of symptoms than the rest of the cohort (p <0.0001). Women showed a higher level of anxiety than men (p = 0.01). A trend for lower level of anxiety was reported by patients who performed habitual physical activity (p = 0.06). A total of 98 (74.2%) patients described worsening of their symptoms during the quarantine period; 94 (71.2%) patients had postponed appointments or visits: they showed a significant worsening of their BS (p =0.01).ConclusionThis study first showed that the COVID-19 quarantine had a significant negative impact on the level of anxiety and BS in MPN patients. We identified female gender, absence of physical activity, the need for frequent visit to the hospital and the absence of a direct access to healthcare staff as the main factors associated to a higher anxiety index and worst BS.