In this week’s episode, we will review a study that uncovers a role for CLCX4 in inducing the two hallmark features of primary myelofibrosis, bone marrow fibrosis and inflammation. We will next examine how genetic predisposition and altered gut microbiome can trigger the development of Precursor B-ALL in mice, and finally, learn how SARS-CoV2 spike proteins activate complement by engaging the alternative pathway, a novel finding which raises the prospect for targeted therapy of COVID-19-associated micro-angiopathy.