Figure 2 Molecular dissection of... | American Society of Hematology

Figure 2

$Figure 2. Molecular dissection of mutational hierarchies using an integrative multisample screening approach. (A) Experimental setup and sorting strategies for dissection of mutational hierarchies for P15. (B) UDS-based profiling of somatic mutations for P15 in a BM sample obtained in 2010, various FACS-sorted subfractions from a BM sample from 2013, as well as xenografted erythroid progenitor cells revealed highly variable VAF patterns (top), representing differential oligoclonal contribution to these compartments (bottom). Cytogenetic lesions were quantified using microsatellite marker analysis. (C) Mutational hierarchy based on sequencing results in (B) showing the initial 5 steps of molecular evolution for P15. (D) Patient-derived xenotransplanted cells (PDX) from P11 showed the presence of an advanced MDS clone in hCD45+ cells resembling the patient’s primary BM but a TET2-only mutated early clone in engrafted hCD19+ cells. (E) Proportion of patients with detectable contribution of MDS-specific mutations to any lymphocytic compartment (primary or xenografted hCD19+ or hCD3+ cells), summarized in supplemental Table 2. Error bars indicate SD. FSC-A, forward scatter area; PI-A, propidium iodide area; PI neg, propidium iodide–negative.$

Molecular dissection of mutational hierarchies using an integrative multisample screening approach. (A) Experimental setup and sorting strategies for dissection of mutational hierarchies for P15. (B) UDS-based profiling of somatic mutations for P15 in a BM sample obtained in 2010, various FACS-sorted subfractions from a BM sample from 2013, as well as xenografted erythroid progenitor cells revealed highly variable VAF patterns (top), representing differential oligoclonal contribution to these compartments (bottom). Cytogenetic lesions were quantified using microsatellite marker analysis. (C) Mutational hierarchy based on sequencing results in (B) showing the initial 5 steps of molecular evolution for P15. (D) Patient-derived xenotransplanted cells (PDX) from P11 showed the presence of an advanced MDS clone in hCD45⁺ cells resembling the patient’s primary BM but a TET2-only mutated early clone in engrafted hCD19⁺ cells. (E) Proportion of patients with detectable contribution of MDS-specific mutations to any lymphocytic compartment (primary or xenografted hCD19⁺ or hCD3⁺ cells), summarized in supplemental Table 2. Error bars indicate SD. FSC-A, forward scatter area; PI-A, propidium iodide area; PI neg, propidium iodide–negative.

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