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It was created by the Prophet (an angel in disguise) approximately 1500 years before the End of Days. When Eirena and her sisters killed their Vizjerei masters, the Prophet found them and cured the curse those mages had bestowed upon the girls with their dying breaths. Foreseeing the dark events of the distant future, the Prophet took the girls with him, forming a sisterhood named Hand of the Prophet. He trained them in magic, augmenting the skills the sisters acquired before. It is not specified how numerous the sisterhood was, but not all of the sisters were actually siblings.
As no mortal man (or, in this case, woman) could survive that long, the Prophet placed the sisters in a dreamless slumber (a kind of stasis spell), with the goal of awakening ages afterwards, and aid the Nephalem against the Evils. He chose one of the sisters, the most powerful (i.e. Eirena), asking all others if they are willing to sacrifice their lives for hers. Before he cast the spell of binding, each of them could leave without any thought of shame, yet only Lysa did so.
Shortly before finding the Nephalem, the hideout has been breached. Demons under Lysa's command killed most, if not all, sisters (except Eirena), some in combat and some in their sleep, and dragged their souls to Pandemonium. They could not break the binding spell, however, and were forced to withdraw, leaving Eirena to wake up alone later.
When Eirena awoke 1500 years later, she encountered the Nephalem. Her companion(s) accompanied her to to the Lair of the Prophet, where Lysa was waiting for her, using the souls of dead sisters as a bait.
After defeating Lysa, Eirena decided to rebuild the sisterhood, in case Sanctuary ever needs their help again, but instead of sleeping for centuries, they would rather pass knowledge from generation to generation.
A Legendary Focus is named after the sisterhood.