Hairy cell leukemia (HCL) is a disease caused by transformed B lymphocytes that repress normal Blood formation. There are several strategies to treat HCL, including chemotherapy or the use of inhibitors, but none of these treatments is curative. Thus, we need to improve our knowledge how HCL cells survive and persist, even under successful treatment. Our aim in HCL leukemia research is to search for specific HCL features that can be targeted to disrupt the HCL life cycle. These features may be enclosed in the tumor cells themselves, but potentially also hidden in their interaction with the surrounding tissue. To detect such features, we compare HCL cells to their normal B cell counterpart, identify the specific perturbations and survival strategies that caused malignant outgrowth, and then estimate whether this may serve as specific vulnerabilities and exploit the possibility to use them as entry points in treating HCL.