<P> Izzie appears in the first episode of Grey's Anatomy, meeting fellow interns Meredith Grey, Cristina Yang, Alex Karev, and George O'Malley . She and George move in with Meredith and become best friends . Izzie's boyfriend, hockey player Hank (Jonathan Scarfe), struggles to accept her new role as a surgeon, and the two break up . Izzie is hurt when Alex exposes her past as a lingerie model . However, the two later go on to begin a friendship and then a romance . Alex experiences sexual dysfunction with Izzie and cheats on her with nurse Olivia Harper (Sarah Utterback). When Izzie finds out, she breaks up with him, though they briefly reunite following a bomb incident at the hospital . Izzie reveals while treating a pregnant teenager that she had a daughter at the age of 16 and gave up for adoption . Izzie falls in love with cardiothoracic patient Denny Duquette (Jeffrey Dean Morgan), and the two become engaged . When Denny's condition deteriorates, Izzie deliberately worsens his health further by cutting his LVAD wire to move him up the donor register . Although Denny receives a new heart, he has a stroke hours later and dies . Izzie is the sole beneficiary of Denny's will, inheriting $8.7 million . She uses the money to open a free clinic at the hospital: the Denny Duquette Memorial Clinic . </P> <P> Izzie disapproves of George's relationship and marriage to orthopedic resident Callie Torres (Sara Ramirez). She and George sleep together, and attempt to keep their liaison a secret . George and resident Miranda Bailey (Chandra Wilson) are the only people aware that Izzie gave birth to a daughter at the age of sixteen; ultimately the child was given up for adoption . He supports Izzie when her daughter Hannah (Liv Hutchings), diagnosed with leukemia, arrives at Seattle Grace Hospital in need of a bone marrow transplant from Izzie . Izzie's feelings for George grow, and she reveals that she has fallen in love with him . When Callie discovers George has been unfaithful, the two separate, and George and Izzie embark on a short - lived relationship, only to discover there is no real chemistry between them . </P> <P> Izzie supports Alex when he discovers his new girlfriend has psychiatric problems, and convinces him to have her committed . She is also handed primary responsibility for the clinic, as Bailey cuts back on her responsibilities . Izzie and Alex go on to rekindle their relationship, though Izzie is concerned when she begins hallucinating Denny . She discovers she has metastatic melanoma (Stage IV) which has spread to her liver, skin, and brain, causing the hallucinations . Her survival chances are estimated at only 5% . She is admitted to Seattle Grace as a patient, and Derek Shepherd (Patrick Dempsey) successfully removes a tumor from her brain . Izzie spends her time in the hospital planning Meredith and Derek's wedding, but when her condition worsens and Derek discovers a second brain tumor, they give the ceremony to Izzie and Alex, who marry in front of all their friends . The procedure to remove the second tumor from Izzie's brain causes her to lose her short - term memory, and although she soon regains it, she flatlines moments later . The fifth season ends with her friends ignoring her DNR order and attempting to resuscitate her, transposed with images of Izzie in an elevator encountering George, who has been in an accident and is also currently flatlining . Though George dies, Izzie is resuscitated and recovers enough to return to work . </P> <P> Izzie makes a treatment error that endangers the life of a patient, and is fired from the hospital's surgical program . Believing Alex is partially to blame, she writes him a Dear John letter and leaves . Izzie later learns that Alex was not responsible for her lost job, and returns to make amends with him, but Meredith informs her that Alex is moving on . Izzie informs Alex that she no longer has cancer . Although he is pleased, Alex officially breaks up with Izzie, telling her that he loves her but deserves better . She leaves Seattle to start fresh . Several episodes later, Alex informs Meredith that Izzie sent divorce papers, which he signs in the episode "How Insensitive". In the sixth - season finale, Alex is shot and asks for Izzie . Imagining that Meredith's half - sister Lexie (Chyler Leigh) is Izzie, he apologizes and asks her never to leave him again . </P>

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