Australian researchers have achieved a significant breakthrough in the treatment of myelofibrosis, a rare and serious form of blood cancer. A team from the South Australian Health and Medical Research Institute (SAHMRI), SA Pathology, and the University of Adelaide has developed a novel targeted therapeutic approach using immunotherapy. This new strategy focuses on directly targeting and removing the abnormal blood cells that drive the disease, moving beyond existing treatments that primarily manage symptoms such as fatigue, pain, and an enlarged spleen. The research, co-led by Professor Daniel Thomas of SAHMRI's Blood Cancer program and Professor Angel Lopez, Head of Human Immunology at SA Pathology, revealed a world-first discovery. They identified not one, but two different molecular targets that can optimally eliminate the culprit cells. Crucially, their findings highlight that Type 1 calreticulin mutations respond differently to treatment compared to Type 2 mutations, paving the way for more precise and tailored therapeutic strategies. This represents a major paradigm shift in how myelofibrosis and related diseases may be treated, harnessing the immune system to specifically recognize and act on disease-causing cells while largely sparing healthy tissue. The study's findings were published in the esteemed international journal *Blood*. This advancement offers substantial hope for improved, more effective, and targeted treatments for patients grappling with this debilitating condition.