LOH in NF1-associated myeloid malignancies and proposed mechanism of interstitial isodisomy. (A) The schematic depicts the 2 different patterns of LOH observed in the tumors. The inactivated NF1 allele (NF-) is marked with an X on the chromosome, while the normal NF1 allele (NF+) is indicated by diagonal hashmarks (////). The interstitial isodisomic and deleted regions can be of maternal or paternal origin. (B) Proposed mechanism for double mitotic recombination during the S/G₂ phase of the cell cycle leading to interstitial uniparental isodisomy in a leukemic-initiating cell. The 4 possible daughter cells are depicted, along with their NF1 genotypes and disomy patterns. Although this example depicts a cell with maternal interstitial isodisomy and NF1 inactivation, paternal interstitial isodisomy was also observed in our study (Figure 1).