Molecular mechanisms of disease progression in pediatric and adult myeloid neoplasms. Leukemic progression of GATA2 deficiency and SAMD9/9L syndromes (top left, blue) are characterized by a high association with monosomy 7. STAG2 mutations are thought to have the ability to rescue progression of GATA2 deficiency.38 Nonrandom loss of chromosome 7 in SAMD9/9L syndromes can be rescued by UPD7q. Somatic LOF SAMD9/9L mutations have also been shown to have ameliorating effects on disease progression. TAM development (top right, yellow) is characterized by trisomy 21 followed by GATA1 mutations. Further acquired somatic mutations in cohesin complex genes and others are thought to drive progression to the leukemic phase. Progression of CH/CCUS/MDS to AML-MR (bottom, red) is driven by a mixture of genetically related but distinct clones (depicted here as A, b, c, d) in a nonlinear fashion termed “parallel evolution.”43 Figure created with Biorender.com.
