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John, is Cross's best friend since childhood and also Alex's partner. Sampson, in Cross is known to have killed Jimmy Hats Galati, Alex's deceased wife's killer. John explains that he didn't want to see Jimmy get away with murdering Alex's wife and also didn't want to see Alex go down a road of revenge and had decided to avenge Alex's wife for him. In another book, Double Cross he is taken hostage while trying to solve the case with Cross's new love interest, Brianna Stone. In earlier books, the first few, he is seen to have had been in love with Nina Childs, who dies in Pop Goes the Weasel causing him to vow to find the killer and get him. In Along Came a Spider some background history is told, one being that when Alex moved to Washington, D.C., after his parents' death (and his move with grandmother Nana Mama) he instantly became friends with Alex. They were known for robbing grocery stores when they were teenagers. Sampson got married in Four Blind Mice to a woman, who he fell in love with, named Billie, despite his reluctance since he is afraid of being a father because his parents were so horrible. It is said that Billie is first and only girl that he has ever made love to. In Alex Cross, Run Sampson informs Alex that Ava has been killed and later assists Bree and Alex in avenging Ava's death.

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