Genetic reversion in an acute myelogenous leukemia cell line from a Fanconi anemia patient with biallelic mutations in BRCA2.

摘要: A 2-year old boy was diagnosed with Fanconi anemia (FA) and acute myeloid leukemia (AML). cell line (termed FA-AML1) established from blast cells obtained after a second relapse successful bone marrow transplant. Histochemical surface marker analysis confirmed that the were derived lineage. Cytogenetic revealed multiple chromosomal aberrations, including ring 7. Stable proliferation of cultured absolutely dependent on presence granulocyte macrophage colony-stimulating factor or interleukin 3. This is first AML successfully FA patient. Remarkably, FA-AML1 appeared to lack characteristic cellular phenotype, i.e., hypersensitivity growth inhibition breakage by cross-linking agent mitomycin C. Genomic DNA patient showed biallelic mutations [8415G>T (K2729N)and 8732C>A (S2835STOP)] in breast cancer susceptibility gene FANCD1/BRCA2 [N. Howlett et al., Science (Wash. DC), 297: 606-609, 2002]. In cells, however, nonsense mutation changed into missense secondary alteration, 8731T>G, resulting 2835E, which restored open-reading frame could explain reverted phenotype these cells. Loss genetic correction during progression may be common late event pathogenesis patients, treatment related. finding suggests novel mechanistic principle tumor based an early caretaker defect.