Figure 4.
Clonal evolution in patients with complex karyotype. (A) SNP genome arrays of AML-MDS patient blasts with complex karyotype and TP53 (p.Y220C; NM_001126112: c.659A>G) mutation (top). Log signal ratio is plotted. Arrows indicate structural abnormalities. Two representative iPSC lines derived from this patient are shown below, wild-type or heterozygous for the TP53 Y220C mutation and normal karyotype in the absence of structural abnormalities. (B) Genotypes of individual iPSCs (across) generated from leukemic blasts of the AML patient in panel A. All iPSC lines derived from these patients have a normal 46,XX karyotype. Karyotypes are shown in supplemental Figure 5B. (C) Comparison of clonal composition (as percentage of total colonies) among CD34+ cell CFUs (40 colonies) and iPSCs (10 colonies). (D) SNP genome arrays of 2 representative iPSCs reprogrammed from an MDS patient with complex karyotype and an inherited Li-Fraumeni TP53 (p.R209fs; NM_000546.5: c.626_627del) mutation. Arrow indicates chromosome 5q deletion in one of the iPSC lines. (E) Genotypes of individual iPSCs (across) generated from Li-Fraumeni MDS patient in panel D. All iPSCs derived from these patients have a normal 46,XX karyotype, and 2 lines had an isolated del(5q), one of which is shown in genome view in (D, bottom). Full karyotypes are shown in supplemental Figure 5C.