Introduction: ... Here, we successfully adapted these techniques to modeling hematologic malignancy for the first time by generating Npm1-Alk in the genome of transplantable hematopoietic stem cells (HSCs). Results and discussion: ... Early animal-modeling efforts with NPM1-ALK (discussed in “Introduction”) left the cell of origin for ALK+ ALCL unclear, and it still has not been definitively revealed. Recently, Malcolm et al shed key light on this question, showing that NPM1-ALK+ thymic precursors use the fusion oncogene to bypass the β-selection checkpoint before moving to the periphery to establish systemic lymphomas.31 By engineering the endogenous translocation into a subset of HSCs, our approach may have allowed recapitulation of this process, as opposed to earlier transgenic approaches placing NPM1-ALK expression under the control of specific T-lineage promoters. Additional evidence also exists for NPM1-ALK arising in early stem or progenitor cells. Trümper et al showed in 1998 ..... READ ARTICLE
Blood Advances DOI:10.1182/bloodadvances.2018025247
Authors: Soumya Sundara Rajan, Lingxiao Li, Mercedes F. Kweh, Kranthi Kunkalla, Amit Dipak Amin, Nitin K. Agarwal, Francisco Vega, Jonathan H. Schatz