FH and hereditary leiomyomatosis and renal cell cancer: Isaacs et al (2005) transfected the FH wild-type lung carcinoma cell line A549 with small interfering RNA (siRNA) targeting FH. The intracellular fumarate level rapidly doubled in treated A549 cells. Although these data support the possibility that reduced FH expression may acutely result in elevated intracellular fumarate, they may not be representative of cellular changes associated with long-term absence of FH expression. However, Pollard et al (2005b) addressed this issue by examining levels of various Kreb's cycle intermediates in uterine leiomyomas from HLRCC patients.