Project description:We performed single cell RNA sequencing to ensure that the engrafted MF cells in NSGS mice retained the molecular properties of the patients cells. ScRNAseq profiles from peripheral blood mononuclear cells (PBMCs) from two independent cord blood and MF patient samples were compared to the engrafted hCD45+ cells from the bone marrow of NSGS mice at 12-weeks post-transplant.
Project description:Myeloproliferative neoplasms (MPNs) are hematological diseases predominantly driven by the JAK2V617F mutation. Progression from chronic-phase MPN to secondary acute myeloid leukemia (sAML) is a severe complication as it dramatically worsens disease prognosis. While sAML transformation is classically linked to MPN clones acquiring additional mutations, the absence of JAK2V617F in sAML cases originating from JAK2-mutant MPNs suggests alternative mechanisms. Utilizing patient samples and in vivo modeling, we establish that sAML clones can emerge independently of JAK2-mutant cells. These leukemic clones undergo positive selection in the pro-inflammatory MPN environment leading to their predominance in the hematopoietic system. Genetic and pharmacological inhibition of IL-12 and TNFa mitigates this competitive advantage. Our data establish a new paradigm and show that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones.
Project description:This SuperSeries is composed of the following subset Series: GSE21948: High Density custom Agilent 44K CGH array analysis of 7q and TET2 region in myelodysplastic/myeloproliferative neoplasms GSE21990: Affymetrix SNP 6.0 array data for myelodysplastic/myeloproliferative neoplasms Refer to individual Series