Figure 4.

Computational Models of Non-Del(5q) MDS Patients with Abnormal Karyotype and Genetic Mutations. MDS patient-specific gene copy number variations, gain-of-function gene mutations, and loss-of-function gene mutations were computationally modeled and lenalidomide treatment digitally simulated. Two-dimensional maps showing intracellular pathways show the mechanisms of lenalidomide resistance in non-del(5q) MDS patients with a trisomy 8 karyotype and a mutation in SF3B1. Arrowed lines indicate agonistic relationship. Barred lines indicate antagnostic relationship. Line colorations are to assist the human eye in discriminating among the pathways. Somatic genes in dark blue boxes indicate copy number variation (CNV) deletions (DEL) derived from cytogenetic abnormalities. Somatic genes in light green indicate CNV amplifications (AMP) derived from cytogenetic abnormalities. Somatic genes with mutations resulting in loss of function (LOF) are indicated in light blue boxes. Somatic genes with mutations resulting in gain of function (GOF) are indicated in dark green boxes.